DOSSIER FOR REGISTRATION OF FOREIGN DRUG

IMPORTED TO CAMBODIA
REGISTRY DRUG DOSSIER
CETIZYTEC

Name and address of registry unit: SARMOT OSCHAR COMPANY LIMITED

Ngoai Trach Village, Tam Hop Commune, Binh

Xuyen District, Vinh Phuc Province

Name and address of manufacturing unit: HA TINH PHARMACEUTICAL JOINT STOCK

COMPANY

167 Ha Huy Tap – Nam Ha Ward – Ha Tinh City –

Ha Tinh Province

Name of drug: CETIZYTEC

Content: Cetirizine dihydrochloride 10mg

Dosage form: Caplet

Classification of drug: Chemical pharmaceutical drug

Kind of registration: First registration

TO: DEPARTMENT OF DRUG AND FOOD

No.8 STREET UNG POKUN (109) – KHAN 7 MAKARA – PNOMPENH –
CAMBODIA.
FAX: (855-23) 880247/ TEL: (855-23)88 02 47

YEAR 2022
 PART I: ADMINISTRATE DATA AND PRODUCT INFORMATION

Table of contents
1. Application Form
2. Letter of Authorization: Applicant Authorization
3. Certifications:
 GMP certificate
 CPP certificate
 Site Master File of manufacture
 Certificate of Analysis of Finished Product (correspond with sample)
4. Labeling: Packaging materials
5. Product Information
6. List of Countries in which the product is registered.
1. APPLICATION FORM
 APPLICATION FORM FOR MARKETING AUTHORIZATION
I. DETAIL OF APPLICANT AND MANUFACTURER
1. Applicants
Name: SARMOT OSCHAR COMPANY LIMITED
Address: Ngoai Trach Village, Tam Hop Commune, Binh Xuyen District, Vinh Phuc
Province

2. Manufacturer’s
Name: Ha Tinh Pharmaceutical Joint Stock Company
Address: No 167 Ha Huy Tap - Nam Ha Ward - Ha Tinh City - Ha Tinh Province
II. DETAIL OF PRODUCT
1. Product name
i. Commercial Name: CETIZYTEC
ii. INN or Generic name:
2. Dosage form and Strength: Each caplet contains:
Cetirizine dihydrochloride 10mg

 Product description: caplet, white color, oval shape, line in the middle, edges are
intact.
3. Quantity of active ingredient(s) and excipients:
 Active ingredient
Cetirizine dihydrochloride 10mg

 Inactive ingredient:

Lactose 100mg

Wheat starch 80mg

Povidone K30 7mg

Sodium Croscarmellose 4mg

Talc 2mg

Sodium Lauryl Sulfate 2mg

Magnesium Stearate 2mg

Hydroxypropyl Methyl cellulose E15 3.5mg

Titanium Dioxide 1mg

Polyethylene Glycol 6000 1mg

4. Indication, Dosage and Administration
i. Indication
In adults and paediatric patients 6 years and above:
 Cetirizine is indicated for the relief of nasal and ocular symptoms of seasonal and
perennial allergic rhinitis.
 Cetirizine is indicated for the relief of symptoms of chronic idiopathic urticaria.
ii. Dosage and Administration
Dosage:
 Adults and children 6 years of age and older take 1 caplet of 10 mg/day or 5 mg x 2
times/day.
5. Packing presentation
- Box of 10 blisters x 10 caplets
6. Shelf-life:
- 36 months since manufacture date.
III. ATTACHED INFORMATION
Certificate of Pharmaceutical Product in the country of Origin 

Manufacturing License GMP-WHO certificate 

Product Information 

Technical Documents 

Samples 

SARMOT OSCHAR COMPANY LIMITED

General Director
2. LETTER OF AUTHORIZATION
 Ha Tinh Pharmaceutical Joint Stock Company
Address: No. 167 Ha Huy Tap – Nam Ha Ward – Ha Tinh
City – Ha Tinh Province – Viet Nam
Tel: +84 239 385 4398

-------------------------------o0o-------------------------------------
Hanoi, May 08rd 2022

LETTER OF AUTHORIZATION
To whom it may concern,

This is to certify that Ha Tinh Pharmaceutical Joint Stock Company (HADIPHAR) existing
and operating under the laws of Vietnam, is the manufacture and exporter of medicines.
The product is manufactured at registered factory, located at – HADIPHAR, following all
current GOOD MANUFACTURING PRACTICE (GMP) regulations recommended by
WHO, and are lawfully exported from Vietnam.

Futher, this is to certify that HADIPHAR authorizes SARMOT OSCHAR COMPANY

LIMITED address: Ngoai Trach Village, Tam Hop Commune, Binh Xuyen District,
Vinh Phuc Province, Viet Nam to act on our behalf in the registration of product name
CETIZYTEC manufactured by HADIPHAR and in the sale and distribution of our
product in the territory of Kingdom of Cambodia.

This authorization is effective immediately until cancelled by written notice.

For and on behalf of HADIPHAR

Genaral Director
3. CERTIFICATION
GMP CERTIFICATE
 CERTIFICATE OF
PHARMACEUTICAL PRODUCT
SITE MASTER FILE
 INDEX

1. GENERAL INFORMATION
1.1. Brief Information
1.2. Pharmaceutical Mfg. Activities
1.3. Other Manufacturing Activities
1.4. Name and Address of the Site
1.5. Type of product manufactured at the site
1.6. Short description of the site
1.7. Employees detail
1.8. External Technical Assistance
1.9. Quality Management System
2. PERSONNEL
2.1. Organization chart
2.2. Qualification, Experience & Responsibilities of Key personnel
2.3. Training (Basic and In-Service)
2.4. Health requirement for personnel engaged in production
2.5. Clothing
3. PREMISES, EQUIPMENT AND SANITATION
3.1. Description of manufacturing areas
3.2. Nature of construction and finishes
3.3. Brief description of ventilation system
3.4. Special area
3.5. Water system
3.6. Maintenance of Premises
3.7. Major production and laboratory equipment
3.8. Maintenance of equipment
3.9. Qualification, Validation and calibration
3.10. Sanitation
4. DOCUMENTATION
4.1. General information
4.2. Other documents related to product quality
4.3. Documents related to environmental control
5. PRODUCTION
5.1. Brief description of production operation
5.2. Handling of material
5.3. Handling of rejected material
5.4. Process Validation
6. QUALITY CONTROL
6.1. Activities of QC department
7. CONTRACT MANUFACTURING AND ANALYSIS
8. DISTRIBUTION, COMPLAINT AND PRODUCT RECALL
8.1. Distribution System
8.2. Handling of complaints
8.3. Handling of product recalls
9. SELF INSPECTION
 CHAPTER I
GENERAL INFORMATION
 CHAPTER I: GENERAL INFORMATION
1. Brief information of the site (including name and address), relation to other sites,
and particularly any information relevant to understand the manufacturing
operations.
Ha Tinh Pharmaceutical Joint Stock Company (herein after HADIPHAR) founded in
1960. The company located at : No. 167 Ha Huy Tap – Nam Ha Ward – Ha Tinh City –
Ha Tinh Province – Viet Nam. The company is well connected with rail, road and sea
transportation network. The company is managed by the Board of Directors. The factory
plant of company can manufacture various dosage form: caplet, blisters caplets, capsule,
lozenge, syrup, oral liquid, ampoule,….The company has more than 400 employees,
including both vocational and bachelor graduated ones. The company also committed to
total quality management. The various raw and packing materials are procured from
approved vendors with all necessary quality documentation as well as received to
warehouse with carefully records as process and kept in quarantine. All raw materials are
carefully test to identify the quality and decide if it is qualified for production or not. The
approved materials shall be marked with complete information and moved to storage
warehouse for production. All products has its own standards dossier in which point out
manufacture process, regulations in each step of production and quality standard of
finished product. The in-process checks are carried out by the Quality Assurance during
the processing of the batch. The semi-finished /finished product are tested as per
specification and testing methods. The testing methods are validated. Instruments and
equipment are calibrated at regular intervals and records are maintained. Internal team
carries out the self-inspection.
2. Pharmaceutical manufacturing activities as licensed by the National authorities
The company has manufacturing license issued by the Vietnam Food Administration -
Ministry of Health as: Certificate Food Safety Conditions No. 30/2019/ATTP-CNGMP
dated June 18th 2019 for food – manufacturing factory.
The company has been certified by Drug Administration of Vietnam to conform GMP
recommended by WHO with certificate 466/GCNQLD dated September 21 th 2016 for
manufacturing chemical medicine.
3. Any other manufacturing activities carried out on the site
Not applicable
4. This site will manufacture Pharmaceutical products and functional food under
following sections:
 Oral liquid: solutions, syrup, suspension,
 Caplets: uncoated, coated (film-, sugar-, enteric-), product not containing β-lactam
 Capsules: Hard/soft gelatin capsule, product not containing β-lactam
 Powder, granule: Oral suspension liquid.
 Effervescent powder, effervescent caplet

5. Name, address and contact of the site:

5.1. Name and Address:
HA TINH PHARMACEUTIC AL JOINT STOCK COMPANY
Address: No. 167 Ha Huy Tap – Nam Ha Ward – Ha Tinh City – Ha Tinh Province – Viet
Nam
5.2. Contact
Email: [email protected]
Website: hadiphar.vn
Key person: Le Quoc Khanh- Director
6. Type of products manufactured:
A. Sterile product
A-1 Liquid dosage form (L.V.P) : YES
A-2 Liquid dosage form (L.V.P) : NO
A-2.1 Aseptically prepared (Bottles and Vials) : NO
A-2.2 Terminally sterilized (Bottle and Vials) : NO
A-2.3 Eye drops : NO
A-3 Semi solid dosage forms : NO
A-4 Solid dosage form : NO
B. Non-sterile product
B-1 Liquid dosage form : YES
B-2 Semi solid dosage form : YES
B-3 Solid dosage form : YES
B-3.1 Unit dose form – caplet : YES
B-3.2 Multi dose form : YES
C. Biological product
C-1 Vaccine : NO
C-2 Sera : NO
C-3 Blood products : NO
C-4 Hormones, enzymes of human or Animal : NO
origin. Genetically engineered products
D. Specifically Toxic & hazardous substance
D-1 Penicillin : NO
D-2 Cephalosporins : NO
D-3 Hormones : NO
D-4 Cytostatics : NO
 D-10 Others : NO

E. Packaging only
E-1 Liquid dosage form : YES
E-2 Semi solid dosage form : YES
E-3 Solid dosage form : YES
F. Contract Manufacturing
F-1 Acceptor : YES
F-2 Giver : NO
G. Contract analysis
G-1 Acceptor : YES
G-2 Giver : NO
H. Drugs for clinical trials : NO
I. Other products
I-1 Veterinary product : NO
I-2 Cosmetic product : NO

7. A short description of the site:

HA TINH PHARMACEUTICAL JOINT STOCK COMPANY locates in Ha Tinh
province, about 340 km from Hanoi capital. The plant area is about 7000m 2, with 04 well-
equipped factories in a non-polluted and well-plan industrial zone. Trees and garden
surrounds the factory plot. The site drawing and pictures are attached in Annex.
8. Number of employees engaged in production, quality control, storage &
distribution
No. Department Managerial Staff Operator/ Total
Technical
worker
1 Production 04 30 300 334
2 Quality Assurance 02 05 0 12
Quality control 02 20 0 22
R&D 01 04 02 07
3 Engineering 03 03 20 26
4 Stores (R.M/P.M) 02 01 0 03
5 Stores (F.G) 01 01 0 02
6 Personnel & Admin 02 06 10 18
 Planning & Sales 04 08 20 32
Finance& Accounting 02 15 0 17
7 General – Director 03 0 0 03
TOTAL 26 93 352 476

9. Quality management system:

9.1. Quality policy
The policy of HADIPHAR is to ensure that the quality of the product is to satisfy the
requirements of customer and society according to current good laboratory and
manufacturing practices.
9.2. Quality Objective
To achieve the desired quality of the product, the quality objectives are:
1. To manufacture the products of high quality that comply to the requirements of
customer and society.
2. To achieve the quality with current Good Manufacturing and Laboratory Practices
3. To maintain the work place and environment neat and clean
4. To apply the corrective changes for implementing the system.
9.3. Responsibility of Q.A
 To authorize the written procedures and other documents including amendments
 To follow the current Good Laboratory practices
 To monitor the compliance of the quality of product with GMP requirements
 To monitor and control of change as per GMP requirements
 To carry out implementation of Corrective and Preventive Actions as part of
improvement Quality system and effectiveness of Quality Management system
 Reject/monitor or approve the supplier’s materials
 To develop risk –based approach to risk-based quality management system.
 Reject/monitor or approve the suppliers
 Inspect and analyze the received materials and manufactured goods as per written
specifications and STPs.
 Validation of processes and calibration of measuring instruments and devices
 Maintain the Hygenic condition in work place and laboratory areas.
 Monitor and control if manufacturing environment
 Conduct the stability testing as per procedure
 Control of Documentation and records
 Handling complaints about products
 Monitoring the release of finished goods.
 Planning of environment control and standardization of working standard and
solution
 Inspect and record control samples
 Training Quality Control personnel according to need
 Take corrective and preventive action in favor of quality of products and receive
materials
 Monitoring and signing on MPCR and BP 2019CR
 9.4. Elements of Q.A system
As describe the quality objectives for achieving the quality following quality system is
incorporated
A ORGANIZATION STRUCTURE
The quality management department is headed by the Quality Manager, a Chief Officer in
charge of Quality Management system, who is highly qualified and experienced industrial
pharmacist. He works totally independently and reports directly only to General Director
of the organization.
The Quality Management System consists of Quality Control and Quality Assurance
Departments, which are managed by sufficient number of qualified and experienced
Analysts, Microbiologist, Pharmacist, etc.
B QUALITY CONTROL RESOURCES
 The quality Control Laboratories have following facilities
 Chemical Analytical Laboratory
 Microbiological Laboratory
 Instrumental Analysis Laboratory
 Control sample and record room
 Other supporting facilities
C QUALITY MANAGEMENT PROCEDURE AND DOCUMENTS
Quality must be a prime consideration in the research and development of a medicine to
assure safety and efficacy. The defined quality criteria vary from country but are similar in
general requirements:
1. Customer focused Organization
Organization depends in their customer and therefore should understand current and future
customer needs, meet customer requirements
2. Leadership
For achieving the leadership creates and maintain the organizational in which people can
become fully involved for achieving the objectives
3. Involvement of People
Using people’s knowledge and experience and through training achieve involvement of
people in operational decisions and process improvement
4. Process approach
Focus in the use of resources in process activity, leading to effective use of people,
equipment, methods and materials
5. System approach to management
Align the processes with the organization’s goal and targets, measure results against key
objectives
6. Continual Improvement
Provide resources, facilities, opportunities and encouragement to people to contribute to
the continual improvement of the process
7. Actual approach to decision making
Take corrective and preventive action by analyzing the data and information to minimize
waste and rework.
8. Mutually Beneficial supplier relationship:
Develop mutual trust, respect and commitment to customer satisfaction and continual
improvement.
DOCUMENTATION
Written documentation of all activities associated with the manufacture and quality control
of Pharmaceuticals covering following aspects is maintained
Building & Premises : Installation, Validation, cleaning and maintenance
Equipment : Installation, Validation, Cleaning & Maintenance
Materials : Specifications, testing, warehousing, use, rejections/disposal
Processing Controls : Individual steps in the process of manufacturing
Finished Goods : Specification, testing, storage, distribution, rejections, disposal
Complaints : Investigation, actions including recall, if necessary
Audit : Internal quality audits
CHAPTER II
PERSONNEL
 1. Qualification, experience and responsibilities of key personnel
Name Education Title Years of Responsibilities
experience
1 Le Quoc Khanh Bachelor of General 30 Overall Management and
Pharmacist Director control day-to-day activities
of the company
2 Tran Van Bachelor of Vice General 27 Office Operations
Chuong Pharmacist Director
3 Nguyen Duc Bachelor of Vice General 27 Factory and Production
Cong Pharmacist Director Operations
4 La The Cuong Bachelor of Planning & 15 Production planning &
Pharmacist Supply material input management
Manager
5 Nguyen Van Bachelor of Head of 10 Quality control and
Chuyen Pharmacist Quality Assurance
Assurance
6 Tran Ngoc Bich Bachelor of Head of 10 Accounting and Finance
Accounting Accounting & operations
Audit
7 Nguyen Phuong Bachelor of Head of 10 Import-Export management
Nam Economics Import-Export
Dep.
8 Nguyen Bich Bachelor of Head of Legal 10 Related to legal issues and
Phuong Pharmacist & Registration registration of products
2. Basic & In-service Training and its records:
2.1. Training needs are identified by comparing the job requirements and the
job capability of the persons doing the job. The deficiencies in the capability of
people are identified and based on that, the training programmers are organized.
This exercise is doned by the HOD and Company head
2.2. All new employees take part in an induction program. This involves and
introduction to the company, its products and policies health, safety regulations and
the concept of good manufacturing and laboratory practices.
Normal job training takes place in work area under the guidance of shop floor
technical supervisor, where specialized training is required, in house courses are
organized or trainees also attend off side courses.
All manufacturing, packaging, engineering, stores, QA, QC staff attend regular
GMP training sessions.
2.3. In service training is imparted to the employees in three different modules
a) GMP/GLP awareness programs, periodic refresher courses on subjects of common
interests.
b) Job related training and training on SOPs.
c) Up-gradation of technical and supervisory knowledge of the personnel with the
latest developments in the field of pharmaceutical technology, quality management
and supervisory techniques.
2.4. Necessary training records are maintained of the training imparted and
evaluation of trainees done.
 Employee’s health is a well-organized program
 The company personnel department is responsible for engaging a well-qualified
medical doctor to get all employees medically examined before employment and
regularly thereafter.
 All employees are routine checked up for their medical fitness and those who are
advised any medical treatment by the examining doctor, are asked to undergo the
medical treatment so advised.
 The departmental supervisors are asked to keep a watch on the health of employees
working in their areas and the employees are also advised to report, any sickness
they have, to their departmental supervisor for necessary action.
 Employees reported sick, can join duty on the certification of the qualified
physician, about their medical fitness.
 Employees working in the sterile operation areas are specifically checked for skin
and other communicable diseases and only after found fit are allowed to work in
the sterile operation area.
 Clothing
 The Company provides suitable washing, change and rest areas for employees and
visitors.
 The dress code for employees is suitably decided to meet the requirement of the job
they perform.
 The dress provided for male employees include lab coat, pant, cap, gloves, mask,
footwear, and necessary safety appliances.
 The dress provided for female employees are taking into consideration the
requirement of the job/G<P and prevailing culture.
 A SOP on clothing clearly describes their routine replacement and laundering.
Personnel are positively discouraged from displaying long hair and nails.
 CHAPTER III
PREMISES, EQUIPMENT &
SANITATION
 CHAPTER III
PREMISES, EQUIPMENT & SANITATION
(A) PREMISES
1. Simple plan or description of manufacturing areas with indication of scale. Plan
of facility is attached.
2. Nature of construction and finishes
The facility is made up of concrete structure, with smooth and hard surfaces, properly
coved corners. Hence, there is no room for accumulation of dusts. All fittings, fixtures are
flushed. Use the wood and asbestos is avoided in the processing areas.
As per the need of the process different kinds of flooring have been provided. e.g.
a) Epoxy painted flooring.
b) Polished stone flooring etc.
c) Polished stone walls, windows & coving.
d) Integrated clean room panel.
3. Brief description of ventilation system
 The requirement of temperature, humidity and type of air is pre-defined based on
the process needs.
 Each of the area is then provided with its environmental requirements with the help
of suitable HVAC system including dehumidification wherever required.
4. Special areas for handling toxic, hazardous & sensitizing materials
We do not handle toxic, hazardous and sensitizing materials in the company.
5. Brief description of water system (schematic drawing of system is desirable)
including sanitation
 As we consider water as the most important ingredient of our process, whether it
remains in the product or not. We use city water, drinking water, soft water,
purified water in production.
 Source of raw water is from city mains.
 Raw water is treated using water softening Company & converted into soft water,
which is used in the boiler, chillers, cooling towers etc.
 Raw water is passed through either a two-pass reverse-osmosis system or de-
mineralizing company & converted into purified water.
 Purified water is further treated using a multicolumn water distillation company to
convert the same into water for injection.
 We have detailed SOPs for Sanitation
6. Maintenance and servicing of the air handling and water system.
 There is an elaborate air handling and water system. We have written procedure,
describing in sufficient details the preventive maintenance system. The records of
such works are kept in the engineering department. Our engineering technicians &
staff know the routine working of the air and water system. They are also trained in
the GMP principles.
 The critical findings from the maintenance reports are made known to the
concerned people. So that they are aware about the issue, if any.
(B) EQUIPMENT
7. Brief description of major production and laboratory
 All equipment have been given distinctive identification number. The history of
maintenance is kept for critical equipment.
 All the machine parts which come in contact with the medicinal products during
processing are made up of SS 316/316L
 Mostly we use SS 316/316L materials for equipment
 The design of the equipment is such that they are suitable to operate, clean and
maintain, they are located in the operational area in such a fashion that they have
ease of operation, cleaning and maintenance. The sizes of the equipment are such
that they can handle the batch size which we are processing.
 In the production areas, we have following Production:
Grinder Fluidized bed dryer
Vacuum mixer Caplet pressing
High speed mixer Film-coating machine
Cubic mixer Gelatin cooking machine
Automatic sieve Encapsulation machine
Granulator Blister filling machine

8. Maintenance and servicing of equipment

 The equipment is maintained by our in-house engineering service department.
However, we also take help from outside service agencies for servicing of weighing
balances and some analytical instrument etc.
 Whenever we are using the services of outside agencies, we enter into a contractual
agreement and follow the same.
 The maintenance technicians who work on the equipment are specifically trained in
carrying out their work without affecting the product quality like isolation of
equipment from materials being processed, post maintenance cleaning and
lubrication etc.
 All work done by engineering people on maintenance etc. is properly recorded and
such records are available for scrutiny at any time.
9. Qualification validation and Calibration
 A validation master plan has been written, clearly defining the scope of activities
like, validation of equipment, processes and facilities etc.
 All existing products are validated by using a retrospective validation method. The
new equipment is validated by using specially designed formats for I.Q., O.Q., P.Q.
etc.
 Generally, if there is any change in the process, then the process is subjected to
revalidation. Similarly, if there is any major change in any process equipment then
the same is subjected to revalidation. Same revalidation policies followed for
HVAC/WATER and other utility services.
 All critical process is identified, product wise and they are validated as a part of
process validation program.
 All batches which are used for validation purpose undergo the same quality tests
before being released for commercial distribution.
 At present, we do not use computerized system in processing.
  Equipment/ Instrument calibration is done by outside expert agencies and they
provide the calibration reports for all the calibration work they have done which
automatically becomes the documented evidence of the calibration work done.
(C) SANITATION
10. Cleaning procedures for manufacturing area and equipment
 We have standard operating procedures for the cleaning of processing and other
areas and equipment used in processing
 We have a schedule for changing of cleaning and sanitizing agents used in the
company.
 The cleaning and sanitizing procedure for areas area validated by the
microbiological test method. The equipment cleaning is validated by the rinse or
swab samples analysis to certify the efficacy of the equipment cleaning method
used.
 CHAPTER IV
DOCUMENTATION
 CHAPTER IV
DOCUMENTATION
1. General information about documentation
 In HADIPHAR, there is a well comprehensive arrangement for the preparation
revision and distribution of various, necessary manufacturing documents. All master
documents are maintained by the Quality Management Department.
 The documents are generally prepared by the concern supervisory staff in the related
department it is checked by a senior staff in the same department and before
finalization it is approved by QA Head and authorized by the head of the company.
 Generally, the documents are reviewed/revised once in two years or if required earlier.
The revisions then made also undergo the same checking apprellipse and authorization
process.
 The distribution and recall of the documents is under the control of Quality
management department.
 All documents are so designed that it gives basic information very clearly to the user
e.g:
 Name of the company
 Location of the company
 Title of the document etc.
Some of the important documents we have are
 Product and process specification
 Raw material specification
 Packaging material specification
 Master production & Control records
 QA release procedure etc.

 All important documents are approved by head of QA department. These

documents if required by the user department, are distributed by QA department as
a controlled copy with proper recording of the same.
 Superseded documents are called back by QA department and one copy of such
document is kept for further reference and all other copies are destroyed and the
destruction is properly recorded.
 Batch/Production related documents are kept at least one year after the expiry of
the product.
 Presently we do not have any electronic or microfilmed documents
2. Other documents related to product quality
In addition to the important documents listed earlier, we also have following documents
namely:
 List of ingredients
 List of standard cleaning materials used
 Various QC procedures/QA procedure
 SOP on training and the records of the training
 SOP on deviation control
 Various processes validations record
 Batch reconciliation record as part of BP 2019CR
3. Documents related to environment control
We also use documents for environmental control like recording of
temperature/humidity/pressure difference in various areas, product recall procedures etc.
 CHAPTER V
PRODUCTION
 PRODUCTION
Brief description of manufacture operation:
All manufacture operations are carried out under the supervision of qualified and
experienced technical staff. They are usually graduate/postgraduate/doctorate in pharmacy
or chemistry with sufficient experience in pharmaceutical manufacture. These supervisory
staff are trained to be always vigilant during the processing activities so that no mistake
can occur. There is an elaborate system of in-process quality control. Production and QA
person take care of this in-process control activities. As the batch manufacturing
progresses the Batch production & Control record (BP 2019CR). Batch reconciliation is
done at critical stages of manufacturing and packaging. In this Company, we produce (a)
uncoated and blisters caplets; (b) capsule; (c) oral liquid; (d)effervescent caplet. The
production flow sheets are appended at the end separately.
Handling of Materials in production
All raw and packaging materials received are first identified by the suppliers lot number
accordingly quarantined, sampled and either approved or rejected. As per the QC
certification, the material gets an Analytical Reference (A.R.) number and then it is
transferred to approve or reject materials storing, as the case may be.
The sampling of materials is done, as per the SOP on sampling by the QC personnel. The
sampled containers are identified as “Sampled” by the way of a separate identification.
All materials are clearly status labeled e.g.
 Name of material
 Under test
 Approved
 Rejected
The raw/packaging materials are issued to production based on a formal written request.
All raw materials are weighed on calibrated weighing balances of suitable capacity in the
presence of a person from QC and production.
All materials which are approved by QC for production purpose are properly identified by
status labelling and such materials are only issued for production after dispensing.
 Control of Bulk Manufacture
All products manufactured have a MPCR. A BP 2019CR is a replica of such approved
MPCR. This clearly describe the method of manufacture, in-process controls required,
against various parameters like weight variation, fiability, disintegration etc. Such findings
are recorded in the BP 2019CR during the process is being carried out.
 CHAPTER VI
QUALITY CONTROL
 QUALITY CONTROL
1. Activities of QC Department
Quality control activity is examination and testing of all incoming materials, which has a
direct or indirect effect on the identity, strength, safety and purity of the pharmaceutical
product.
The QC is also responsible for the in-process checks and the release of the finished
pharmaceuticals for distribution.
Semi-finished and finished products are released for packing and for sale respectively by
QC after ascertaining QA clearance as per following norm.
Samples of each batch of semi-finished products are drawn by QA person at specific
intervals during entire batch production per the respective specifications (Pharmacopoeial
or in-house or both). Analytical details and results are recorded in test protocols and
certificates of analysis. The bulk batch is change over to packaging department only after
confirming clearance by QC and QA. Upon completion of packing, reconciliation is
carried out and packing statement sheet mentioning batch details and the packed quantity
is filled and sent to QA for apprellipse. QA person verifies the BP 2019CR and then gives
“Release for Sale or distribution”.
Finished products failing to meet the specified standards are quarantined and kept under
“HOLD” for further investigation or reprocessing as the case may be.
Quality control department controls the preparation, revision, distribution and recall of all
Pharmaceutical documents.
 CHAPTER VII
CONTRACT
MANUFACTURING
AND ANALYSIS
 CONTRACT MANUFACTURING & ANALYSIS
The company has a policy to undertake contract manufacturing of other companies if
mutually agreeable to both
No contract analysis is undertaken by the company for any other company.
 CHAPTER VIII
DISTRIBUTION,
COMPLAINT
AND PRODUCT RECALL
 DISTRIBUTION, COMPLAINTS AND PRODUCT RECALL
1. Agreement for recording system for distribution
We have a well-built and highly secured warehouse for storage of the finished foods for
distribution or sale
The storage conditions are the warehouse is maintained as per the requirement of the
product e.g. air-conditioned storage, low temperature/low humidity storage etc.
We have products requiring refrigerated storage.
All the materials are stored only on the clean PVC pallets, avoiding there by direct contact
with the floor.
All the finished product shippers are properly labeled giving the details about the product
name and batch number. This helps in proper identification of the finished products at any
time.
No rejected material is coming in the area where only released finished products are
stored. The rejected materials are kept totally isolated in the separate area always under
lock and key.
The finished good are distributed as per the marketing requisition/orders on first in-first
out basic. A complete record of the finished goods distribution is maintained and where
the full batch is completely distributed the information for the whole batch distribution
details include the list of purchasers, date of the sale and quantity, and other commercial
information. This data is available product wise/batch wise. Such historical batch
distribution details are retrievable immediately.
2. Arrangement for handling of complaints
Market complaints are normally raised by doctor, consumers, medical representatives or
DAV officials.
We have a SOP on handling of market complaint in the following way:
1. Receiving the complaints
2. Recording all available data of the product/batch and nature of the complaint.
3. Evaluating the complaints
4. Compare it with retained sample of the same product/batch
5. Identify the reasons for the complaint
6. Take corrective action
7. Communicate with the complainant
8. Record completely the investigations and remedy action in the complaint file
9. Review the market complaints trend at regular intervals.
3. Arrangement for handling product recalls
Recall procedure is followed as per SOP. Recall is initiated by the Quality Assurance
department. The seriousness of the error is discussed in a joint meeting consisting of
representative from QC, production, formulation development & the top management. The
recall is instituted by sending a recall circular by fastest mode of communication available
at that time, to all concern people at all concern locations. All efforts are made to receive
and collect the maximum number of units of the batch at the point of availability.
If required, the QC head communicates to the DAV authorities. The involvement of DAV
authorities depends upon the seriousness of the reason for the product recall. We try to go
to the level of retailers for recalling a product. But generally it is restricted to wholesale.
Reasons for product recall are thoroughly investigates by the management & properly
recorded.
Based on the finding of these report necessary corrective actions are taken to avoid the
recurrence of such cases in the future.
 CHAPTER IX
SELF-INSPECTION
 SHORT DESCRIPTION OF THE SELF-INSPECTION PROGRAM
We have a SOP for the self-inspection program. It is carried out every 6 months. The area
covered includes production, QC laboratory, stores, engineering etc. the self-inspection is
carried out by a team headed by Quality Manager.
The parameters cover compliance with cGMP, cGLP, cGSP SOPs, Hygiene, BP 2019CR.
Safety, validation, etc.
The audit report is summarized and an action plan is prepared. The concerned department
head initiates the actions required and informs to the Quality manager.
These reports are reviewed regularly for compliance and improvement.
PRODUCT INFORMATION
 1. TRADE NAME OF THE MEDICINAL PRODUCT:
CETIZYTEC (caplets)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION:
 ACTIVE INGREDIENT:
Cetirizine dihydrochloride 10mg

 QUANTITATIVE COMPOSITION:
Each blisters caplets contains:
Cetirizine dihydrochloride 10mg

Lactose 100mg

Wheat starch 80mg

Povidone K30 7mg

Sodium Croscarmellose 4mg

Talc 2mg

Sodium Lauryl Sulfate 2mg

Magnesium Stearate 2mg

Hydroxypropyl Methylcellulose E15 3.5mg

Titanium Dioxide 1mg

Polyethylene Glycol 6000 1mg

3. PHARMACEUTICAL FORM
Caplet
4. CLINICAL CHARACTERISTIC
 THERAPEUTIC INDICATION:
In adults and paediatric patients 6 years and above:
 Cetirizine is indicated for the relief of nasal and ocular symptoms of seasonal and
perennial allergic rhinitis.
 Cetirizine is indicated for the relief of symptoms of chronic idiopathic urticaria.
Usage: Taken orally with water CETIZYTEC should be taken before meals. If taken after
meals, the drug may be slowly absorbed.
Dosage:
  Adults and children 6 years of age and older take 1 let of 10 mg/day or 5 mg x 2
times/day.
Contraindications:
Hypersensitivity to Cetirizine dihydrochloride or to any of the ingredients.
Warning and important when using drugs.
Ask doctor before using this medicine:
If you have liver disease or are careful, include alcoholic liver disease.
CETIZYTEC is not toxic at therapeutic doses, and when used under the guidance of a
physician. However, overdose of Cetirizine dihydrochloride can cause liver failure.
Taking multiple products containing Cetirizine dihydrochloride at the same time can lead
to harmful consequences (such as Cetirizine dihydrochloride overdose).
Do not exceed the prescribed dose.
You should avoid drinking too much caffeine (e.g. coffee, tea and some cans) when using
this product.
Using drugs for pregnant and lactating women
Pregnant:
For cetirizine prospectively collected data on pregnancy outcomes do not suggest potential
for maternal or fontal/embryonic toxicity above background rates.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,
embryonal/fetal development, parturition or postnatal development. Caution should be
exercised when prescribing to pregnant women.
Breastfeeding period:
Cetirizine passes into breast milk. A risk of side effects in breastfed infants cannot be
excluded. Cetirizine is excreted in human milk at concentrations representing 25% to 90%
of those measured in plasma, depending on sampling time after administration. Therefore,
caution should be exercised when prescribing cetirizine to lactating women.
Effects of the drug on the ability to drive and use machine.
Objective measurements of driving ability, sleep latency and assembly line performance
have not demonstrated any clinically relevant effects at the recommended dose of 10 mg.
However, patients who experience somnolence should refrain from driving, engaging in
potentially hazardous activities or operating machinery. They should not exceed the
recommended dose and should take their response to the medicinal product into account.
Drug interactions and incompatibilities.
Due to the pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no
interactions are expected with this antihistamine. Actually, neither pharmacodynamic nor
significant pharmacokinetic interaction was reported in drug-drug interactions studies
performed, notably with pseudoephedrine or theophylline (400 mg/day).
The extent of absorption of cetirizine is not reduced with food, although the rate of
absorption is decreased.
In sensitive patients, the concurrent use of alcohol or other CNS depressants may cause
additional reductions in alertness and impairment of performance, although cetirizine does
not potentiate the effect of alcohol (0.5 g/L blood levels).
Undesirable effects.
Clinical studies have shown that cetirizine at the recommended dosage has minor
undesirable effects on the CNS, including somnolence, fatigue, dizziness and headache. In
some cases, paradoxical CNS stimulation has been reported.
Although cetirizine is a selective antagonist of peripheral H1-receptors and is relatively
free of anticholinergic activity, isolated cases of micturition difficulty, eye
accommodation disorders and dry mouth have been reported.
Instances of abnormal hepatic function with elevated hepatic enzymes accompanied by
elevated bilirubin have been reported. Mostly these resolves upon discontinuation of the
treatment with cetirizine dihydrochloride.
Overdose and treatment.
For Cetirizine dihydrochloride
 Symptom:
Symptoms observed after an overdose of cetirizine are mainly associated with CNS effects
or with effects that could suggest an anticholinergic effect.
Adverse events reported after an intake of at least 5 times the recommended daily dose is:
confusion, diarrhea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness,
sedation, somnolence, stupor, tachycardia, tremor, and urinary retention.
 To solve:
There is no known specific antidote to cetirizine.
Should overdose occur, symptomatic or supportive treatment is recommended. Gastric
lavage may be considered shortly after ingestion of the drug.
Cetirizine is not effectively removed by hemodialysis.

5. PHARMACOLOGICAL PROPERTIES
 PHARMACODYNAMICS
Cetirizine dihydrochloride:
In addition to its anti-H1 effect, cetirizine was shown to display anti-allergic activities: at a
dose of 10 mg once or twice daily, it inhibits the late phase recruitment of eosinophils, in
the skin and conjunctiva of atopic subjects submitted to allergen challenge.
 Clinical efficacy and safety
Studies in healthy volunteers show that cetirizine, at doses of 5 and 10 mg strongly
inhibits the wheal and flare reactions induced by very high concentrations of histamine
into the skin, but the correlation with efficacy is not established.
In a six-week, placebo-controlled study of 186 patients with allergic rhinitis and
concomitant mild to moderate asthma, cetirizine 10 mg once daily improved rhinitis
symptoms and did not alter pulmonary function. This study supports the safety of
administering cetirizine to allergic patients with mild to moderate asthma.
In a placebo-controlled study, cetirizine given at the high daily dose of 60 mg for seven
days did not cause statistically significant prolongation of QT interval.
At the recommended dosage, cetirizine has demonstrated that it improves the quality of
life of patients with perennial and seasonal allergic rhinitis.
 Paediatric population
In a 35-day study in children aged 5 to 12, no tolerance to the antihistaminic effect
(suppression of wheal and flare) of cetirizine was found. When a treatment with cetirizine
is stopped after repeated administration, the skin recovers its normal reactivity to
histamine within 3 days.

 PHARMACOKINETICS
Cetirizine dihydrochloride:
The steady - state peak plasma concentrations are approximately 300 ng/mL and is
achieved within 1.0 ± 0.5 h. The distribution of pharmacokinetic parameters such as peak
plasma concentration (Cmax) and area under curve (AUC), is unimodal.
The extent of absorption of cetirizine is not reduced with food, although the rate of
absorption is decreased. The extent of bioavailability is similar when cetirizine is given as
solutions, capsules or caplet.

6. PHARMACEUTICAL CHARACTERISTICS:
 SHELF-LIFE:
36 months since manufacturing date.
 STORAGE:
Store in a cool, dry place, protected from sun light, temperature below 30°C
 PACKAGING:
Box of 10 blisters x 10 caplets
 INSTRUCTION FOR USE/HANDLE:
Handle with care
7. MARKETING AUTHORIZATION HOLDER:
Name: SARMOT OSCHAR COMPANY LIMITED
Address: Ngoai Trach Village, Tam Hop Commune, Binh Xuyen District, Vinh Phuc
Province
8. MANUFACTURER:
Name: HA TINH PHARMACEUTICAL JOINT STOCK COMPANY
Address: No 167 Ha Huy Tap - Nam Ha Ward - Ha Tinh City - Ha Tinh Province
PART II: QUALITY
 TABLE OF CONTENT
Section A: Table of content
Section B: Quality Overall Summary
Section C: Body of data
Drug Substance
Drug product
Section D: Key Literature references
 SECTION A:
TABLE OF CONTENT
 TABLE OF CONTENT
Ingredient Quantity
Cetirizine dihydrochloride 10mg

Lactose 100mg

Wheat starch 80mg

Povidone K30 7mg

Sodium Croscarmellose 4mg

Talc 2mg

Sodium Lauryl Sulfate 2mg

Magnesium Stearate 2mg

Hydroxypropyl Methylcellulose E15 3.5mg

Titanium Dioxide 1mg

Polyethylene Glycol 6000 1mg

 SECTION B:
QUALITY OVERALL SUMMARY
 SECTION B: QUALITY OVERALL SUMMARY (QOS)
No. PARAMETERS COMPONENTS
S Drug substance
S1 General information
1.1 Nomenclature
Cetirizine dihydrochloride INN: Cetirizine dihydrochloride
IUPAC name: 2-(2-{4-[(4-chlorophenyl)
(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid
ATC code: R06AE07
1.2 Structure
Cetirizine dihydrochloride

Molecular formula; C21H25ClN2O3

Molecular weight: 388.888
CAS no.: 83881-51-0
1.3 General properties
Cetirizine dihydrochloride Detail in “S1.3 General properties”- Cetirizine
dihydrochloride
S2 Manufacture
2.1 Manufacture(s)
Cetirizine dihydrochloride Zhejiang Xianju Pharmaceutical Co.,Ltd
Address: No.3 Donghai Fourth Avenue, Duqiao Medical and
Chemical Industry Zone, Linhai, Zhejiang, China
2.2 Manufacture process No required (to generic drug)
and control
2.3 Material control No required (to generic drug)
2.4 Control of critical No required (to generic drug)
steps and intermediates
2.5 Process validation No required (to generic drug)
and/or evaluation
 2.6 Process development No required (to generic drug)
S3 Characterization
3.1 Explanation of
structure and/or others
specification
Cetirizine dihydrochloride is the carboxylic acid metabolite of hydroxyzine. It is a
selective, peripheral H1 receptor antagonist. It is a long-lasting
antihistamine. It does not appear to have the same adverse
cardiac effects as the other nonsedating H1 antihistamines;
however, additional data are required. Indicated for allergic
rhinitis and chronic urticaria
3.2 Impurities
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
S4 Control of drug substance
4.1 Specification
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
4.2 Analytical procedure
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
S5 Reference standards or
materials
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
S6 Container closure system
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
S7 Stability
Cetirizine dihydrochloride As required in monograph: Cetirizine dihydrochloride – USP
40
P DRUG PRODUCT
P1 Description and Description: caplet, white color, oval shape, line in the middle,
composition edges are intact.
Dosage form and characteristic: caplet
Packaging: Box of 10 blisters x 10 caplets
Composition:
No. Ingredient Quantity
 1 Cetirizine dihydrochloride 10mg
2 Lactose 100mg

3 Wheat starch 80mg

4 Povidone K30 7mg

5 Sodium Croscarmellose 4mg

6 Talc 2mg

7 Sodium Lauryl Sulfate 2mg

8 Magnesium Stearate 2mg

9 Hydroxypropyl 3.5mg
Methylcellulose E15

10 Titanium Dioxide 1mg

11 Polyethylene Glycol 6000 1mg

P2 Pharmaceutical
development
2.1 Research and Not applicable
development information
2.2 Components of the Detail in “P2.2 Components of the drug product”
drug product
2.3 Finished product Detail in “P2.3 Finished product”
2.4 Development of Detail in “P 2.4 Development of manufacture process”
manufacture process
2.5 Container closure CETIZYTEC is 10 caplets per one blister, box of 10 blisters
system with usage instruction leaflet inserted in box paper.
2.6 Microbial property No required
2.7 Compatibility Do not use diluted solvent
P3 Manufacture
3.1 Batch formula Batch formula for 1 batch of 100.000 caplets
No. Raw Materials Quantity (g)

1 Cetirizine dihydrochloride 1000g

2 Lactose 10000g
 3 Wheat starch 8000g

4 Povidone K30 700g

5 Sodium Croscarmellose 400g

6 Talc 200g

7 Sodium Lauryl Sulfate 200g

8 Magnesium Stearate 200g

9 Hydroxypropyl 350mg
Methylcellulose E15

10 Titanium Dioxide 100g

11 Polyethylene Glycol 6000 100g

3.2 Manufacturing process Detail in CETIZYTEC, P3. Manufacture

and process control
3.3 Control of critical Detail in CETIZYTEC, P3. Manufacture
steps and intermediates
3.4 Process validation Detail in CETIZYTEC, P3. Manufacture
and/or evaluation
P4 Control of excipients
4.1 Specifications No. Ingredient Standard
1 Lactose USP 40

2 Wheat starch USP 40

3 Povidone K30 USP 40

4 Sodium Croscarmellose USP 40

5 Talc USP 40

6 Sodium Lauryl Sulfate USP 40

7 Magnesium Stearate USP 40

8 Hydroxypropyl USP 40
Methylcellulose E15

9 Titanium Dioxide USP40

10 Polyethylene Glycol 6000 USP 40

 4.2 Analytical procedure Detail in “P4.2 Analytical procedure”
4.3 Excipient origin from Not applicable
human/animal
4.4 New excipient No applicable
P5 Control of finished
product
5.1 Standard of finished As In house standard: IHS-115-110
product
5.2 Analytical procedures As In house standard: IHS-115-110
P6 Reference standards As in CETIZYTEC, P6. Reference standards
P7 Container closure system CETIZYTEC is 10 caplets per one blister, box of 10 blisters
with usage instruction leaflet inserted in box paper.
P8 Stability As in CETIZYTEC, P8. Stability

P9 Product interchangeability Not required

equivalence evidence
SECTION C: BODY OF DATA
 SECTION C: BODY OF DATA
Table of contents
1. Drug substance
S1 General information
S2 Manufacture
S3 Characterization
S4 Control of drug substance
S5 Reference standards or materials
S6 Container closure system
S7 Stability
2. Drug product (P1P9)
P1 Description and composition
P2 Pharmaceutical development
P3 Manufacture
P4 Control of excipients
P5 Control of finished product
P6 Reference standards or materials
P7 Container closure system
P8 Product stability
P9 Product interchangeability
DRUG SUBSTANCE
(S1  S7)
 BODY DATA Cetirizine
HADIPHAR
S. DRUG SUBSTANCE dihydrochloride

S1. GENERAL INFORMATION

Cetirizine dihydrochloride
S1.1. Nomenclature
Generic name: Cetirizine dihydrochloride
IUPAC name: 2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid
ATC code: R06AE07
S1.2. Structure

Molecular formula; C21H25ClN2O3

Molecular weight: 388.888
CAS no.: 83881-51-0
S1.3 General Properties
White to beige powder

S2. MANUFACTURE
S2.1. Manufacturer:
Zhejiang Xianju Pharmaceutical Co.Ltd
Address: No.3 Donghai Fourth Avenue, Duqiao Medical and Chemical Industry Zone,
Linhai, Zhejiang, China
S2.2. Manufacture process and control
No required (to generic drug)
S2.3. Material control
No required (to generic drug)
S2.4. Control of critical steps and intermediates
No required (to generic drug)
S2.5. Process validation and/or evaluation
No required (to generic drug)
S2.6. Process development
No required (to generic drug)
S3. CHARACTERISATION
S3.1. Explanation of structure and/or others specification
CETIZYTEC is the carboxylic acid metabolite of hydroxyzine. It is a selective, peripheral
H1 receptor antagonist. It is a long-lasting antihistamine. It does not appear to have the
same adverse cardiac effects as the other nonsedating H1 antihistamines; however,
additional data are required. Indicated for allergic rhinitis and chronic urticaria
S3.2. Impurities
Satisfied standard of reference of Cetirizine dihydrochloride – USP 40
S4. CONTROL OF DRUG SUBSTANCE
Satisfied standard of reference of Cetirizine dihydrochloride – USP 40
S4.2. Analytical procedure
Satisfied standard of reference of Cetirizine dihydrochloride – USP 40
S4.3. Analytical procedure assessment
Not applicable
S4.4. Batch analysis
Certificate of Analysis issued by Manufacturer’s and Quality Control Laboratory attached.
S4.5. Quality standard demonstration
No required (to generic drug)
S5. REFERENCE STANDARDS OR MATERIAL
Cetirizine dihydrochloride
Source: National Institute of Drug Quality Control
Control No: 0311022.03
S6. CONTAINER CLOSURE SYSTEM
Cetirizine dihydrochloride is packed every 10kg in 2 layer of PE bags, in carton box.
S7. STABILITY
As per Zhejiang Xianju Pharmaceutical Co.,Ltd
Address: No.3 Donghai Fourth Avenue, Duqiao Medical and Chemical Industry Zone,
Linhai, Zhejiang, China
DRUG PRODUCT
(P1  P9)
DESCRIPTION AND
COMPOSITION
(P1)
 DESCRIPTION AND COMPOSITION
1. Description
 Name of product: CETIZYTEC
 Description: caplet, white color, oval shape, line in the middle, edges are intact.
 Dosage form: caplet
 Presentation: Box of 10 blisters x 10 caplets
 Storage: Dry and cool place, below 300C, keep away from sunlight.
 Shelf life: 36 months
2. Composition of each caplet:
No Ingredient Amount Function Specification
.

1 Cetirizine dihydrochloride 10mg Active Ingredient USP 40

2 Lactose 100mg Excipient USP 40

3 Wheat starch 80mg Excipient USP 40

4 Povidone K30 7mg Excipient, USP 40

preservative agent
5 Sodium Croscarmellose 4mg Excipient, USP 40
preservative agent
6 Talc 2mg Excipient, USP 40
preservative agent
7 Sodium Lauryl Sulfate 2mg Excipient, USP 40
preservative agent
8 Magnesium Stearate 2mg Excipient, USP 40
preservative agent
9 Hydroxypropyl 3.5mg Excipient USP40
Methylcellulose E15

10 Titanium Dioxide 1mg Excipient USP 40

11 Polyethylene Glycol 6000 1mg Excipient Manufacture

3. Presentation:
Box of 10 blisters x 10 caplets
PHARMACEUTICAL
DEVELOPMENT
(P2)
 PHARMACEUTICAL DEVELOPMENT
CETIZYTEC
1. Composition
No Ingredient Amount Function Specification
.

1 Cetirizine dihydrochloride 10mg Active Ingredient USP 40

2 Lactose 100mg Excipient USP 40

3 Wheat starch 80mg Excipient USP 40

4 Povidone K30 7mg Excipient, USP 40

preservative agent
5 Sodium Croscarmellose 4mg Excipient, USP 40
preservative agent
6 Talc 2mg Excipient, USP 40
preservative agent
7 Sodium Lauryl Sulfate 2mg Excipient, USP 40
preservative agent
8 Magnesium Stearate 2mg Excipient, USP 40
preservative agent
9 Hydroxypropyl 3.5mg Excipient USP40
Methylcellulose E15

10 Titanium Dioxide 1mg Excipient USP 40

11 Polyethylene Glycol 6000 1mg Excipient Manufacture

* Ethanol does not exist in finished product

 Compatibility:
+ Active ingredient with excipients: Cetirizine dihydrochloride not incompatible with
Lactose, Wheat starch, Povidone K30, Sodium Croscarmellose, Talc, Sodium
Lauryl Sulfate, Magnesium Stearate, Hydroxypropyl Methylcellulose E15,
Titanium Dioxide, Polyethylene Glycol 6000
+ Between excipients: no incompatibility between excipients in formula.
 References: Vidal 2010, MIMS 2010, Hanbook pharmaceutical excipients.
 Function of ingredients in formula:
No. Ingredient Amount Function

1 Cetirizine dihydrochloride 10mg Active Ingredient

 2 Lactose 100mg Excipient

3 Wheat starch 80mg Excipient

4 Povidone K30 7mg Excipient, preservative

agent
5 Sodium Croscarmellose 4mg Excipient, preservative
agent
6 Talc 2mg Excipient, preservative
agent
7 Sodium Lauryl Sulfate 2mg Excipient, preservative
agent
8 Magnesium Stearate 2mg Excipient, preservative
agent
9 Hydroxypropyl 3.5mg Excipient
Methylcellulose E15

10 Titanium Dioxide 1mg Excipient

11 Polyethylene Glycol 6000 1mg Excipient

2. Finished product
Active ingredient specification:
 Cetirizine dihydrochloride: white to beige powder Soluble in water, DMSO,
ethanol, and methanol., melting at 110-115 degrees.
Selection of excipients: not compatible with other ingredient of product.
Selection of manufacturing method:
Dosage method: granule powder manufacture method, including: grinding material,
dual mixing, grind wet granule, grain fixing, sticky excipient mixing, drying,
packing on automatic packing machine.
Selection of packing method: Through stability testing process, it is reported that
packing method: PE/AL/PE film can ensure the quality of product.
3.Research and development of the finished product:
 Cetirizine dihydrochloride relevant to its action: assay, uniformity of the mass.
 Block diagram of the research and development of product:
 Research at pilot scale: conduct 3 pilot batch to test and conduct necessary
adjustment to optimal manufacture formula and methods.
 After get pilot-scale product at stable quality and pass requirements of product
standard, upgrade to commercial scale batch.
 Dosage method: granule powder manufacture method, including: grinding material,
dual mixing, grind wet granule, grain fixing, sticky excipient mixing, drying,
packing on automatic packing machine.
 Manufacture condition: Temperature: 20-250C, room humidity 40-60%
 Accelerated shelf life
Accelerated shelf life monitoring and long
monitoring term shelf-life
(stability)

Lab scale batches with Selection of optimal 3 pilot-scale batch

Shelf-life
different formulations formulation production

Long term stability Long term stability

studies studies

Technology transfer to 3 commercial-scale 3-production

Product approved scale batches
product unit batches

Validation Validation Prospective validation

sampling and
registration
 The optimal formulation had been selected based on the result from research
studies of stability, uniformity and productibility of the batches as above
mentioned.
4. Container closure system
 Raw materials, packaging materials are to be control as per specifications.
 Product is packed in Al blisters of 10 caplets, box of 10 blisters
 The stability of this package system should be monitored to verify that package
system meets the specified request
5. Compatibility
As per references and observation from production and stability studies, there is no
incompatibility between the components and the composition and the manufacturing
processes whatsoever.
MANUFACTURE
(P3)
 MANUFACTURE PROCESS
1. Batch formula for 100.000 caplets
No. Raw Materials Quantity (g)

1 Cetirizine dihydrochloride 1000g

2 Lactose 10000g

3 Wheat starch 8000g

4 Povidone K30 700g

5 Sodium Croscarmellose 400g

6 Talc 200g

7 Sodium Lauryl Sulfate 200g

8 Magnesium Stearate 200g

9 Hydroxypropyl Methylcellulose E15 350mg

10 Titanium Dioxide 100g

11 Polyethylene Glycol 6000 100g

2. Manufacturing process and process control

2.1. Flow chart of manufacturing process
2.2. Machine and equipment

No. Machine Quantity (unit) Country of Origin

1 Scale 300kg 3 Japan

2 Scale 1.2kg 3 Japan

3 Scale 300g 1 Vietnam

4 Sieve 3 Vietnam

5 Grinding machine 1 Vietnam

6 High-speed Mixer 1 Vietnam

7 Oscillating granulator 1 Vietnam

8 Fluid bed dryer 1 Vietnam

 9 Cubic Mixer 1 Vietnam

10 Packing machine 1 China

11 Vacuum machine 1 China

12 Aluminum tank 1 Vietnam

13 Inox tank 3 Vietnam

14 Inox ladle 5 Vietnam

2.3. Description of the manufacturing process

2.4. General conditions
The manufacturing process will only start when the working area, equipment,
personnel and raw materials involved are in compliance with the Good Manufacture
Practices (GMP’s), namely:
a) The working area should be perfectly clean and free from any document, material or
component non-required for the operation being performed;
b) The equipment should be perfectly clean and duly identified;
c) The personnel should wear personal protection, including cap, gloves, boots mask and
glasses;
d) The starting materials should be previously approved by the Quality Control;
e) All documents and equipment necessary for the batch manufacturing should be in the
working area.
2.5. Detailed of manufacturing procedure:
2.5.1. Material weighing: Weigh all qualified materials as formula quantity.
2.5.2. Dual-mixing

Mixing formula for 100.000 caplets

No. Raw Materials Quantity (g)

1 Cetirizine dihydrochloride 1000g

2 Lactose 10000g

3 Wheat starch 8000g

4 Povidone K30 700g

5 Sodium Croscarmellose 400g

6 Talc 200g

7 Sodium Lauryl Sulfate 200g

 8 Magnesium Stearate 200g

9 Hydroxypropyl Methylcellulose E15 350mg

10 Titanium Dioxide 100g

11 Polyethylene Glycol 6000 100g

Preparation

 Grind perfectly all ingredients through sift through 0.5mm sieve, then weigh
folowing the formula
 Mix mixture in co-volume principle . Sift through sieve of 0.10mm, then load
this mixture to high-speed mixer and mix in 07 mins to get a homogeneous powder
mixture.
2.5.3. Liquid mixing

No. Raw Materials Quantity (g)

1 Dry grain collected from last steps

2 Liquid mixture from last step

Preparation

 Put dry grain collected from last step into cubic mixer, operating mixing in 10
minutes.
 Stop the machine, take the dry grain out into plastic tank (A)
 Divide the powder mixture into 10 parts, gradually put each part into the tank of
distilled water, stir until the powder dissolve completely. Then load the other part
and continue to stir and mix. Repeat until the total amount is dissolved completely.
 Take samples for QC test of semi-finished product
2.5.4. Caplet pressing
 Operate caplet pressing by appropriate machine. During process, regularly check the
appearance of caplet, check the average weight of caplet every 15 mins. The theory
average weight of one caplet is about 146,7mg. The weight of one caplet should be in
range ± 7.5% average of 1 caplet.
 Check the firmness and dissolution every 60 mins.
2.5.5. Blister filling
 Packing room must be cleaned , room temperature 25ºC ± 5ºC, RH: 60% ±5%
 Filling blisters by blisters-filling machine and check regularly the quantity packed,
appearance of caplets, the closeness of blisters, batch number and expired date.
2.5.6. Box packing
 Pack in specification complying to the packing specification, each package provided
with the respective package leaflet
 Send an average sample of finished product to Quality Control and keep the finished
products in quarantine until apprcircle.
2.6. In-process quality control
 Control of raw materials:

All ingredients and excipients must complies with standard applied for each as stated.

 Control during weighing:

Check the cleanliness of the premise and relevant equipment.

Check the name, label and amount weigh of the relevant raw materials as per written
instruction.

Double check

 Control during mixing

Check and get line clearance before starting and after finishing process.

Check and control mixing time as per Specification.

 Control during granulation preparation:

Check and get line clearance before starting and after finishing process.

Check and control mesh size, drying, temperature setting of drying, residual moisture
content.

 Control during bottle packing:

Check and get line clearance before starting and after finishing process.

Check and control botlle packing machine setting and tool as per written instruction
(mortar size, marks, pressure setting, filling depth, production rate)

Check and control packing process as per written instruction (apperance, foreign matter,
closeness of bottle, average volumne of one bottle and volumne variation,).

 Control during packaging:

Check and get line clearance before starting and after finishing process.

Check the packaging materials as per Specifications

Check the control packed contents as per Specification.

 3. Control of critical steps and intermediates
Manufacture Stage Test Tester

Raw materials  Quality QC department

 Quantity Manufacture Supervisor

Material weighing  Identification of materials
QC Supervisor

Sticky excipients  Conform with formula Manufacture Supervisor

mixture preparation  Quantity of ingredients

 Homogeneity of mixture Manufacture Supervisor

Dual-mixing
 Mixing time

 Quantity of powder mixture Manufacture Supervisor

 Mixing time
Liquid dissolving QC Supervisor
 Uniformity of liquid solution
after mixing

 Identification QC Department
Semi-finished product  Assay
Test  Appearance of
 Homogeneous of liquid solution

 Average volumne of bottle Manufacture Supervisor

 Appearance
QC Supervisor
 Uniformity of volumne
Bottle packing  Closeness of cap
 Identification
 Assay
 Microbial test

 Complies to packing Manufacture Supervisor

Box packaging specification
 Batch No. and expired date
Test before warehouse  As Basic Standard QC Department
storage Annoucement
Test method:
No. Items Test content Test method
1 Granules  Assay Quantitative determination
2 Caplet  Appearance Visual inspection
 Identification
3 Finished product Qualitative determination
 Uniformity of weight
 Assay Scales
 Dissolution
Quantitative method

4. Process validation
Table of content
1. Introduction
2. Objective
3. Scope of validation process
4. Process description
5. Responsibility
6. Pre-requisites
7. Approach
8. Number of run & schedule
9. Critical process steps
10. Equipment and calibration status
11. General Acceptance criteria
12. Sampling and testing plan with acceptance criteria
13. Appendix
14. References
 1. INTRODUCTION
The following is the process validation for the manufacturing process of caplet of
HADIPHAR
2. OBJECTIVE
The purpose of process validation is to provide evidence that the procedure followed by
manufacturer in caplets manufacturing, is performing as per provided SOP’s specifications
and manufacturing documents.
3. SCOPE OF VALIDATION PROCESS
Nowadays, in this expanding era of the regulatory control in pharmaceutical industry
mostly concern with process validation activity based on the way of documentation and
testing of product such as in process testing by this caplet manufacturer can say that their
formulas and process working as per their expectation and specifications. This ensures that
caplet is homogeneous and reliable.
Definition of process validation
Process validation is the documented evidence that the process. operated within
established parameters, can perform effectively and reproducibly to produce a medical
product meeting its predetermined specifications and quality attribute.
Pic/s code of GMP-Annex
15
.(2.3.4 Pics VMP)
 4. RESPONSIBILITY
DEPARTMENT RESPONSIBILITY
Quality Assurance Establishes and apprellipse of validation
protocols and reports
Manage require documents and procedures
To perform process validation by monitoring.
Sampling, testing, auditing of specific
manufacturing process for compliance with
specification and requirements
Engineering To install, qualify and certify all equipment,
facilities as well as support system
To develop master validation plan
Quality Control To conduct test
Review protocols and reports as per
requirement
R&D To design and qualify, manufacturing process
within specification and requirement
Manufacturing Operates and maintain all facilities, equipment
and support system and manufacturing process
with in specifications

5. PRE-REQUISITE
Pre-requisites Status Reference Date
Checking date Expiry date
Qualification of Qualified but has Validation 07/2010
critical services and been checked document
utilities before process
Qualification and Qualified and CL948-00 06/2008
calibration of calibrated but has
equipment been checked
before process
Qualification of Qualified KT029-01 15/05/2008
facilities and
environment
Validation of test Validated but has Registration 24/05/2008
method been checked document
Master batch record Approved TV447-01 21/04/2010
Training of personal Trained Document of 16/08/2009 16/08/2010
 training

NOTE: All documents and SOPs are approved and signed by QA manager before
manufacturing process.
6. APPROACH
There are mainly four approaches for the process validation
Prospective validation 
Concurrent validation 
Retrospective validation 
Re-validation 
Prospective validation
In this approach, validation carried out before the production of the product that intended
for the sale in market. Further, in this validation, process divided in various steps. Each
step analyzed experimentally or theoretically to get proper knowledge about critical
process parameters and their effect on product quality.
The reason to do validation by prospective approach is that before the manufacturing of
caplet manufacturing can predict the critical process point, their effect on product quality
and manufacturer can solve obstacles which may arise during process.
7. NUMBER OF RUNS & SCHEDULE
For prospective validation, three different batches of caplet will be taken into
consideration
BATCH NUMBER BATCH SIZE SCHEDULE DATE
RPB2054 100.000 caplets Nov 2017
RPB2055 100.000 caplets Nov 2017
RPB2056 100.000 caplets Nov 2017

8. CRITICAL PROCESS STEPS

Step Process risk assessment Impact assessment
Weighing and grinding Medium Non critical
Making sticky excipient Higher Critical
mixture
Dual mixing Higher Critical
Making wet mixture Higher Critical
Wet-granulating Higher Critical
Drying Higher Critical
 Fixing dry granule Higher Critical
Out-mixing Higher Critical
Packing Low Non critical
Labelling and packaging Low Non critical

HIGHER RISK: The step during which the severity and probability of occurrence harm to
product quality, purity, uniformity is high.
MEDIUM RISK: The step during which severity and probability of occurrence harm to
product quality, purity, uniformity is high.
LOWER RISK: The step during which the severity and probability of occurrence harm to
product quality, purity, uniformity is low.
Critical step: The step which changes form of the product, which effect product Quality,
uniformity, identity, purity.
9. EQUIPMENTS AND CALIBRATION STATUS
Process step Name of Calibration Qualification plan Cleaning
equipment status validation
IQ OQ PQ Monitor
Weighing and Scale set, Calibrated   
grinding grinding and
kneading
machine
Making sticky Inox tank, cradle Calibrated     
excipient
mixture
Dual mixing High speed mixer Calibrated     
TBGP002
Making wet High speed mixer Calibrated     
mixture TBGP002
Wet- High speed Calibrated     
granulating Oscillating
granulator
TBGP007
Drying Fluid bed dryer Calibrated     
TBGP003
Fixing dry High speed Calibrated     
granule Oscillating
granulator
TBGP007
Out-mixing Cubic mixer Calibrated     
TBGP 022
Packing Packing machine Calibrated     
ZPW23B

10. GENERAL ACCEPTANCE CRITERIA

If there is, any deviation during manufacturing process, it should be resolved and properly
documented.
All batches must meet to the product specification.
By use of process capability or standard deviation process is not varies too much is
checked.
11. SAMPLING AND TESTING WITH ACCEPTANCE CRITERIA
If there is, any deviation during manufacture process it should be resolved and properly
documented
All batches must meet to the product specification.
By use of process capability or standard deviation process is not varies too much is
checked.
12. SAMPLING AND TESTING PLAN WITH ACCEPTANCE CRITERIA
PROCESS SAMPLING PLAN TESTING PLAN ACCEPTANCE
STEP CRITERIA
Weighing and Place of sampling: Size of All ingredient after
grinding take 3 samples on top, granule/powder after kneading must go
in the middle and at grinding through sieve of
bottom of mixture 0.5mm
Sample size:
100g/each
Method of taking
sample: Random
Dual mixing Place of sampling: Homogeneity of The powder mixture
take samples at 9 mixture after mixing should
place: 8 corners and 1 be homogeneous,
in the center of the no clot, no clumps
mixer
Time of sampling: at 3
time: 3 – 10– 7
minutes of mixing
Sample size: 20g/each
Method of taking
sample: Random
Drying Place of sampling: at Humidity of dried 0.5-10%
granules sampling place of fluid granules
bed dryer
Time of sampling: at 3
time: after drying 15-
20-210minutes
Sample size: 20g/each
Method of taking
sample: Random
Out-mixing Place of sampling: Homogeneity of The powder mixture
take samples at 9 mixture after mixing should
place: 8 corners and 1 be homogeneous,
in the center of the no clot, no clumps
mixer
Time of sampling: at 3
time: 10 – 110– 20
minutes of mixing
Sample size: 20g/each
Method of taking
sample: Random
Place of sampling: Assay of active As per In house
random position ingredients in Standard
mixture
Time of sampling:
after finish mixing
process
Sample size: 20g/each
Method of taking
sample: Random
CONTROL OF EXCIPIENTS
(P4)
 CONTROL OF EXCIPIENTS
P4. CONTROL OF EXCIPIENTS
P4.1. EXCIPIENTS SPECIFICATION
No Ingredient Amount Function Specification
.

1 Lactose 100mg Excipient USP 40

2 Wheat starch 80mg Excipient USP 40

3 Povidone K30 7mg Excipient, USP 40

preservative agent
4 Sodium Croscarmellose 4mg Excipient, USP 40
preservative agent
5 Talc 2mg Excipient, USP 40
preservative agent
6 Sodium Lauryl Sulfate 2mg Excipient, USP 40
preservative agent
7 Magnesium Stearate 2mg Excipient, USP 40
preservative agent
8 Hydroxypropyl 3.5mg Excipient USP40
Methylcellulose E15

9 Titanium Dioxide 1mg Excipient USP 40

10 Polyethylene Glycol 1mg Excipient Manufacture

6000

P4.2. ANALYTICAL METHOD

No. Ingredient Specification

1 Lactose USP 40

2 Wheat starch USP 40

3 Povidone K30 USP 40

4 Sodium Croscarmellose USP 40

5 Talc USP 40

6 Sodium Lauryl Sulfate USP 40

 7 Magnesium Stearate USP 40

8 Hydroxypropyl Methylcellulose E15 USP40

9 Titanium Dioxide USP 40

10 Polyethylene Glycol 6000 Manufacture

P.4.3. EXCIPIENTS ORIGINATE FROM HUMAN AND ANIMALS

Not applicable

P.4.4. NEW EXCIPIENTS

Not applicable
CONTROL OF FINISHED
PRODUCT (P5)
P5. CONTROL OF FINISHED PRODUCT

P.5.1 IN HOUSE STANDARD

In house standard: 0350-B-011-13

P.5.2. ANALYTICAL METHOD

In house standard: 0350-B-011-13

 IN HOUSE STANDARD
HADIPHAR CETIZYTEC
No.: 0350-B-011-13

1. SPECIFICATION

1.1. Composition of caplets:

Cetirizine dihydrochloride Ten milligrams 10mg

(Excipients: : Cetirizine dihydrochloride are not incompatible with Lactose, Wheat starch,
Povidone K30, Sodium Croscarmellose, Talc, Sodium Lauryl Sulfate, Magnesium
Stearate, Hydroxypropyl Methylcellulose E15, Titanium Dioxide, Polyethylene Glycol
6000)
1.2. Ingredient standard

No Ingredient Amount Function Specification

.

1 Cetirizine dihydrochloride 10mg Active Ingredient USP 40

2 Lactose 100mg Excipient USP 40

3 Wheat starch 80mg Excipient USP 40

4 Povidone K30 7mg Excipient, USP 40

preservative agent
5 Sodium Croscarmellose 4mg Excipient, USP 40
preservative agent
6 Talc 2mg Excipient, USP 40
preservative agent
7 Sodium Lauryl Sulfate 2mg Excipient, USP 40
preservative agent
8 Magnesium Stearate 2mg Excipient, USP 40
preservative agent
9 Hydroxypropyl 3.5mg Excipient USP40
Methylcellulose E15

10 Titanium Dioxide 1mg Excipient USP 40

11 Polyethylene Glycol 6000 1mg Excipient Manufacture

1.3. Standard of finished product

1.3.1. Specification: Caplet, white color, oval shape, line in the middle, edges are intact.

1.3.2. Identification: Positive for Cetirizine dihydrochloride

1.3.3. Disintegration: No more than 30 minutes.

1.3.4. Uniformity of weight: In twenty random indiovidual mass, no more than 2

individual mass deviates more than 5% and none deviates more than 10% average weight
of caplet.

1.3.5. Assay:

Assay of

 Cetirizine dihydrochloride 90.0 - 110.0%

compared to the amount stated on label, count based on average weight of one caplet.

2. ANALYSIS METHOD:

2.1. Specification: by sensory test, finished product must satisfy requirements.

2.2. Identification:

•  A. Infrared Absorption 〈197K〉
•  B. The retention time of the major peak of the Sample solution corresponds to that of
the levocetirizine peak of the System suitability solution, as obtained in the test
for Enantiomeric Purity.
•  C. Identification Tests—General 〈191〉, Chloride: Meets the requirements

INFRARED ABSORPTION
Seven methods are indicated for the preparation of previously dried test specimens and
Reference Standards for analysis. The reference 〈197K〉 in a monograph signifies that the
substance under examination is mixed intimately with potassium bromide. The
reference 〈197M〉 in a monograph signifies that the substance under examination is finely
ground and dispersed in mineral oil. The reference 〈197F〉 in a monograph signifies that
the substance under examination is suspended neat between suitable (for example, sodium
chloride or potassium bromide) plates. The reference 〈197S〉 signifies that a solution of
designated concentration is prepared in the solvent specified in the individual monograph,
and the solution is examined in 0.1-mm cells unless a different cell path length is specified
in the individual monograph. The reference 〈197A〉 signifies that the substance under
examination is intimately in contact with an internal reflection element for attenuated total
reflectance (ATR) analysis. The reference 〈197E〉 signifies that the substance under
examination is pressed as a thin sample against a suitable plate for IR microscopic
analysis. The reference 〈197D〉 in a monograph signifies that the substance under
examination is mixed intimately with an IR-transparent material and transferred to a
sample container for diffuse reflection (DR) analysis. The ATR 〈197A〉 and
the 〈197E〉 techniques can be used as alternative methods for 〈197K〉, 〈197M〉, 〈197F〉,
and 〈197S〉 where testing is performed qualitatively and the Reference Standard spectra
are similarly obtained.
Record the spectra of the test specimen and the corresponding USP Reference Standard
over the range from about 2.6 µm to 15 µm (3800 cm–1 to 650 cm–1) unless otherwise
specified in the individual monograph. The IR absorption spectrum of the preparation of
the test specimen, previously dried under conditions specified for the corresponding
Reference Standard unless otherwise specified, or unless the Reference Standard is to be
used without drying, exhibits maxima only at the same wavelengths as that of a similar
preparation of the corresponding USP Reference Standard.
Differences that may be observed in the spectra so obtained sometimes are attributed to
the presence of polymorphs, which are not always acceptable
(see Procedure under 〈854〉). Unless otherwise directed in the individual monograph,
therefore, continue as follows. If a difference appears in the IR spectra of the analyte and
the standard, dissolve equal portions of the test specimen and the Reference Standard in
equal volumes of a suitable solvent, evaporate the solution to dryness in similar containers
under identical conditions, and repeat the test on the residues.
ULTRAVIOLET ABSORPTION
The reference 〈197U〉 in a monograph signifies that a test solution and a Standard
solution are examined spectrophotometrically, in 1-cm cells, over the spectral range from
200 to 400 nm unless otherwise specified in the individual monograph.
Dissolve a portion of the substance under examination in the designated Medium to
obtain a test solution having the concentration specified in the monograph
for Solution. Similarly prepare a Standard solution containing the corresponding USP
Reference Standard.
Record and compare the spectra concomitantly obtained for the test solution and the
Standard solution. Calculate absorptivities and/or absorbance ratios where these criteria
are included in an individual monograph. Unless otherwise specified, absorbances
indicated for these calculations are those measured at the maximum absorbance at about
the wavelength specified in the individual monograph. Where the absorbance is to be
measured at about the specified wavelength other than that of maximum absorbance, the
abbreviations (min) and (sh) are used to indicate a minimum and shoulder, respectively, in
an absorption spectrum. The requirements are met if the UV absorption spectra of the test
solution and the Standard solution exhibit maxima and minima at the same wavelengths
and absorptivities and/or absorbance ratios are within specified limits.

2.3. Disintegration: As per USP 40-Disintegration

This general chapter is harmonized with the corresponding texts of the European

Pharmacopoeia and/or the Japanese Pharmacopoeia. The texts of these pharmacopeias
are therefore interchangeable, and the methods of the European Pharmacopoeia and/or
the Japanese Pharmacopoeia may be used for demonstration of compliance instead of the
present general chapter. These pharmacopeias have undertaken not to make any unilateral
change to this harmonized chapter.

Portions of the present general chapter text that are national USP text, and therefore not
part of the harmonized text, are marked with symbols (♦♦) to specify this fact.

This test is provided to determine whether caplets or capsules disintegrate within the
prescribed time when placed in a liquid medium at the experimental conditions presented
below. ♦Compliance with the limits on Disintegration stated in the individual monographs
is required except where the label states that the caplets or capsules are intended for use as
troches, or are to be chewed, or are designed as extended-release dosage forms or delayed-
release dosage forms. Determine the type of units under test from the labeling and from
observation, and apply the appropriate procedure to 6 or more dosage units.♦
For the purposes of this test, disintegration does not imply complete solution of the unit or
even of its active constituent. Complete disintegration is defined as that state in which any
residue of the unit, except fragments of insoluble coating or capsule shell, remaining on
the screen of the test apparatus or adhering to the lower surface of the disk, if used, is a
soft mass having no palpably firm core.

APPARATUS

The apparatus consists of a basket-rack assembly, a 1000-mL, low-form beaker, 138 to

160 mm in height and having an inside diameter of 97 to 115 mm for the immersion fluid,
a thermostatic arrangement for heating the fluid between 35° and 39°, and a device for
raising and lowering the basket in the immersion fluid at a constant frequency rate
between 29 and 32 cycles per minute through a distance of not less than 53 mm and not
more than 57 mm. The volume of the fluid in the vessel is such that at the highest point of
the upward stroke the wire mesh remains at least 15 mm below the surface of the fluid and
descends to not less than 25 mm from the bottom of the vessel on the downward stroke. At
no time should the top of the basket-rack assembly become submerged. The time required
for the upward stroke is equal to the time required for the downward stroke, and the
change in stroke direction is a smooth transition, rather than an abrupt reversal of motion.
The basket-rack assembly moves vertically along its axis. There is no appreciable
horizontal motion or movement of the axis from the vertical.

Basket-Rack Assembly

The basket-rack assembly consists of six open-ended transparent tubes, each 77.5 ± 2.5
mm long and having an inside diameter of 20.7 to 23 mm and a wall 1.0 to 2.8 mm thick;
the tubes are held in a vertical position by two plates, each 88 to 92 mm in diameter and 5
to 8.5 mm in thickness, with six holes, each 22 to 26 mm in diameter, equidistant from the
center of the plate and equally spaced from one another. Attached to the under surface of
the lower plate is a woven stainless steel wire cloth, which has a plain square weave with
1.8- to 2.2-mm apertures and with a wire diameter of 0.57 to 0.66 mm. The parts of the
apparatus are assembled and rigidly held by means of three bolts passing through the two
plates. A suitable means is provided to suspend the basket-rack assembly from the raising
and lowering device using a point on its axis.

The design of the basket-rack assembly may be varied somewhat, provided the
specifications for the glass tubes and the screen mesh size are maintained. The basket-rack
assembly conforms to the dimensions found in Figure 1.

Disks

The use of disks is permitted only where specified or allowed ♦in the monograph. If
specified in the individual monograph,♦ each tube is provided with a cylindrical disk 9.5 ±
0.15 mm thick and 20.7 ± 0.15 mm in diameter. The disk is made of a suitable transparent
plastic material having a specific gravity of between 1.18 and 1.20. Five parallel 2 ± 0.1-
mm holes extend between the ends of the cylinder. One of the holes is centered on the
cylindrical axis. The other holes are centered 6 ± 0.2 mm from the axis on imaginary lines
perpendicular to the axis and parallel to each other. Four identical trapezoidal-shaped
planes are cut into the wall of the cylinder, nearly perpendicular to the ends of the
cylinder. The trapezoidal shape is symmetrical; its parallel sides coincide with the ends of
the cylinder and are parallel to an imaginary line connecting the centers of two adjacent
holes 6 mm from the cylindrical axis. The parallel side of the trapezoid on the bottom of
the cylinder has a length of 1.6 ± 0.1 mm, and its bottom edges lie at a depth of 1.5 to 1.8
mm from the cylinder's circumference. The parallel side of the trapezoid on the top of the
cylinder has a length of 9.4 ± 0.2 mm, and its center lies at a depth of 2.6 ± 0.1 mm from
the cylinder's circumference. All surfaces of the disk are smooth. If the use of disks is
specified ♦in the individual monograph♦, add a disk to each tube, and operate the apparatus
as directed under Procedure. The disks conform to dimensions found in Figure 11.

Figure 1. Disintegration apparatus. (All dimensions are expressed in mm.)

PROCEDURE
♦
Uncoated Caplet
♦Place 1 dosage unit in each of the six tubes of the basket and, if prescribed, add a disk.
Operate the apparatus, using ♦water or♦ the specified medium as the immersion fluid,
maintained at 37 ± 2°. At the end of the time limit specified ♦in the monograph,♦ lift the
basket from the fluid, and observe the caplets: all of the caplets have disintegrated
completely. If 1 or 2 caplets fail to disintegrate completely, repeat the test on 10 additional
caplets. The requirement is met if not fewer than 16 of the total of 18 caplets tested are
disintegrated.
♦
Plain-Coated Caplet

Apply the test for Uncoated Caplet, operating the apparatus for the time specified in the
individual monograph.

Acceptance criteria: No more than 30 minutes

2.4. Uniformity of weight:

As per Vietnam Pharmacopoeia IV- Appendix 11.3 –

Weigh individually twenty units taken at random, and determine the average mass. Not
more than two of the individual masses deviate from the average mass by more than 5%
and none deviates by more than twice that percentage.
2.5. Assay

•  Procedure
Mobile phase:  Acetonitrile, water, and 1 M sulfuric acid (93: 6.6: 0.4)
Standard solution:  0.05 mg/mL of USP Levocetirizine Dihydrochloride RS in Mobile
phase
Sample solution:  0.05 mg/mL of Levocetirizine Dihydrochloride in Mobile phase
Chromatographic system 
(See Chromatography 〈621〉 , System Suitability.)
Mode:  LC
Detector:  UV 230 nm
Column:  4.6-mm × 25-cm; 5-µm packing L3
Column temperature:  30°
Flow rate:  1 mL/min
Injection volume:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 1.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of levocetirizine dihydrochloride (C21H25ClN2O3 ·2HCl) in the
portion of Levocetirizine Dihydrochloride taken:
Result = ( r U / r S ) × ( C S / C U ) × 100
r U = peak response of levocetirizine from the Sample solution
r S = peak response of levocetirizine from the Standard solution
C S = concentration of USP Levocetirizine Dihydrochloride RS in the Standard
solution (mg/mL)
C U = concentration of Levocetirizine Dihydrochloride in the Sample
solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the dried basis
IMPURITIES
Change to read:
•   Residue on Ignition 〈281〉 : NMT   0.2%   (RB 1-Apr-2016)
Change to read:
•  Organic Impurities
Mobile phase:  Acetonitrile, water, and 1 M sulfuric acid (93: 6.6: 0.4)
System suitability solution:  0.2 mg/mL of USP Levocetirizine Dihydrochloride RS and
0.2 µg/mL each of USP Levocetirizine Amide RS and USP Chlorobenzhydryl Piperazine
RS in Mobile phase. Use the solution within 16 h.
Standard solution:  0.2 µg/mL each of USP Levocetirizine Dihydrochloride RS, USP
Levocetirizine Amide RS, and USP Chlorobenzhydryl Piperazine RS in Mobile phase.
Use the solution within 16 h.
Sample solution:  200 µg/mL of Levocetirizine Dihydrochloride in Mobile phase. Use the
solution within 16 h.
Chromatographic system 
(See Chromatography 〈621〉 , System Suitability.)
Mode:  LC
Detector:  UV 230 nm
Column:  4.6-mm × 25-cm; 5-µm packing L3
Column temperature:  30°
Flow rate:  1 mL/min
Injection volume:  20 µL
Run time:  3 times the retention time of levocetirizine
System suitability 
Samples:  System suitability solution and Standard solution
[Note— See Table 1 for the relative retention times. ]
Suitability requirements 
Resolution:  NLT 3.0 between levocetirizine and chlorobenzhydryl piperazine, System
suitability solution
Tailing factor:  NMT 2.0 for levocetirizine, System suitability solution
Relative standard deviation:  NMT 5.0% for levocetirizine, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of levocetirizine amide or chlorobenzhydryl piperazine in the
portion of Levocetirizine Dihydrochloride taken:
Result = ( r U / r S ) × ( C S / C U ) × 100
r U = peak response of levocetirizine amide or chlorobenzhydryl piperazine from
the Sample solution
r S = peak response of levocetirizine amide or chlorobenzhydryl piperazine from
the Standard solution
C S = concentration of USP Levocetirizine Amide RS or USP Chlorobenzhydryl
Piperazine RS in the Standard solution (µg/mL)
C U = concentration of Levocetirizine Dihydrochloride in the Sample
solution (µg/mL)
Calculate the percentage of any unspecified impurity in the portion of
Levocetirizine Dihydrochloride taken:
Result = ( r U / r S ) × ( C S / C U ) × 100
r U = peak response of any unspecified impurity from the Sample solution
r S = peak response of levocetirizine from the Standard solution
C S = concentration of USP Levocetirizine Dihydrochloride RS in the Standard
solution (µg/mL)
C U = concentration of Levocetirizine Dihydrochloride in the Sample
solution (µg/mL)
Acceptance criteria:  See Table 1.
Table 1
 Relative Acceptance
Retention Criteria,
Name Time NMT (%)

Levocetirizine
—
dihydrochloride 1.0

Chlorobenzhydryl piperazine 1.3  0.2%   (RB 1-Apr-2016)

Levocetirizine amide 2.5  0.2%   (RB 1-Apr-2016)

Any individual
unspecified —
impurity  0.1%   (RB 1-Apr-2016)

Total impurities —  0.5%   (RB 1-Apr-2016)

Change to read:
•  Enantiomeric Purity
Analyze the solutions within 24 h of preparation.
Mobile phase:  Prepare a mixture of chromatographic solvent hexane and absolute
alcohol (95:5). Add 2 mL of trifluoroacetic acid per L of mixture.
System suitability solution:  5 mg/mL of USP Cetirizine Hydrochloride RS in absolute
alcohol
Sensitivity solution:  0.05 mg/mL of USP Levocetirizine Dihydrochloride RS in absolute
alcohol
Sample solution:  5 mg/mL of Levocetirizine Dihydrochloride in absolute alcohol
Chromatographic system 
(See Chromatography 〈621〉 , System Suitability.)
Mode:  LC
Detector:  UV 230 nm
Column:  4.6-mm × 25-cm; 5-µm packing L40
Column temperature:  30°
Flow rate:  1.5 mL/min
Injection volume:  10 µL
System suitability 
Samples:  System suitability solution and Sensitivity solution
[Note— The relative retention times for the S-enantiomer (of cetirizine) and
levocetirizine, which is the R-enantiomer of cetirizine, are about 0.7 and 1.0,
respectively. ]
Suitability requirements 
Resolution:  NLT 1.5 between the S-enantiomer and levocetirizine, System suitability
solution
Signal-to-noise ratio:  NLT 10 for levocetirizine, Sensitivity solution
Analysis 
Sample:  Sample solution
Calculate the percentage of the S-enantiomer in the portion of
Levocetirizine Dihydrochloride taken:
Result = ( r U / r T ) × 100
r U = peak response for the S-enantiomer from the Sample solution
r T = sum of all the peak responses for the S-enantiomer and levocetirizine from
the Sample solution
Acceptance criteria:  NMT   2.0%   (RB 1-Apr-2016) of the S-enantiomer
SPECIFIC TESTS
Change to read:
•   Loss on Drying 〈731〉
Analysis:  Dry at 105° to constant weight.
Acceptance criteria:  NMT   1.0%   (RB 1-Apr-2016)
•   pH 〈791〉
Sample solution:  50 mg/mL of Levocetirizine Dihydrochloride in water
Acceptance criteria:  1.2–1.8

3. PACKAGING, LABELING, STORAGE AND SHELF LIFE:

 Packaging: product is packed in blisters of 10 caplets, protect from sunlight

 Label: clear, conform to requirements
 Storage: dry and cool place, below 300C, protect from sunlight.
 Shelf life: 36 months since manufacture date.
REFERENCE STANDARDS OF
MATERIALS
(P6)
 REFERENCE STANDARDS OF MATERIALS

No Ingredient Amount Function Specification

.

1 Cetirizine dihydrochloride 10mg Active Ingredient USP 40

2 Lactose 100mg Excipient USP 40

3 Wheat starch 80mg Excipient USP 40

4 Povidone K30 7mg Excipient, USP 40

preservative agent
5 Sodium Croscarmellose 4mg Excipient, USP 40
preservative agent
6 Talc 2mg Excipient, USP 40
preservative agent
7 Sodium Lauryl Sulfate 2mg Excipient, USP 40
preservative agent
8 Magnesium Stearate 2mg Excipient, USP 40
preservative agent
9 Hydroxypropyl 3.5mg Excipient USP40
Methylcellulose E15

10 Titanium Dioxide 1mg Excipient USP 40

11 Polyethylene Glycol 6000 1mg Excipient Manufacture

CONTAINER CLOSURE SYSTEM
(P7)
P7. CONTAINER CLOSURE SYSTEM
P7.1. Description of container closure system
CETIZYTEC is packed in complex PE/Al/PE film, printed information of product, batch
no., manufacture date and expired date, Each box of 10 blisters x 10 caplets
P7.2. Standard of container label
 BASIC STANDARD
P7.CONTAINER
HADIPHAR CETIZYTEC
CLOSURE SYSTEM
PAPER BOX
 
1. Technical specification
1.1. Specification :  
-     Box of carton paper Ivory 350, rectangular shape, smooth and homogeneous surface,
no wrinkle or tearing,  no with hole perforation , no dust and dirt , the content printed on
box conforms to the content approved by Department of Drug management - Ministry of
Health . 
1.2. Size  :  
- Length : 115.0 mm   ± 0.5 mm.         
- Width : 65.0 mm ± 0.5 mm.         
- Height : 56.0 mm ± 0.5 mm         
1.3. Printings  content:  
- Color : conform to the sample design file.
- Printing quality: homogeneous and clear, no ink smudge, no fade .         
- Printing content: conform to the sample design file, approved by Department of Drug
management - Ministry of Health . 
1.4. Weight : ≥ 6.9 g  
2. Test method
2.1. Specification : By sensory test and comparation to standard sample, tested sample
should satisfy requirements.      
2.2. Size : Use ruler (mm division) to measure samples taken . :      
- Length : 115.0 mm   ± 0.5 mm.         
- Width : 65.0 mm ± 0.5 mm.         
- Height: 56.0 mm ± 0.5 mm         
       Sample that excess the measures above will be not qualify and not used for
packaging.
2.3. Printings content :    
Compared tested sample and satandard sample, with requirements as follow :
- Color : conform to the sample design file.
- Printing quality: homogeneous and clear, no ink smudge, no fade .         
- Printing content: conform to the sample design file, approved by Department of Drug
management - Ministry of Health . 
2.4. Weight : Get 10 boxes and weight. The tested sample must have the weight as
required in standard
3. Packaging :
-   Pack label in the bag PE, closed tight,  on the label have  information : name of the
manufacturer, name of product, quantity, batch no., packaging standard, manufacture date.
4. Storage: Place in dry cool warehouse
 BASIC STANDARD
P7.CONTAINER
HADIPHAR CETIZYTEC
CLOSURE SYSTEM
PVC/ALUMINUM BLISTER

A. ALUMINUM FILM TECHNICAL STANDARD

1. Technical requirements

No. Criteria Requirements

1.1 Appearance The aluminum film is clean, shine and smooth surface,
no dust or dirt, no insect, no scratch, wrinkles.
The inner side shine and smooth, with a thin
homogeneous heat-glue layer
The outer side print the label content of product, clear
ink printing, no fade or smudge.
1.2 Measurement Wide: 250mm ± 1mm
Thickness: 0.026mm ± 8.0%
1.3 Weight 60g/m2 ± 8.0%
1.4 Printing Color: as regist sample design.
Printing quality: homogeneous, sharp and clear, not
smudge or fade
1.5 Limit of microbiological Total aerobic microbial count: ≤190CFU/100cm2
Total yeast and mold count: ≤19CFU/100cm2
Not allowed:
Escherichia Coli
Salmonella
Pseudomonas aeruginosa
Staphylococcus aureus
B.
 B. PVC BLISTER FILM
1. Technical standard
No. Criteria Requirements
1.1 Appearance The PVC film is made from Aluminum plastic film, no
color, homogeneous thickness, smooth surface, no dust
or dirt, no insect, no scratch, wrinkles, no hole.
1.2 Measurement Wide: 250mm ± 1mm
Thickness: 0.274mm ± 5.0%
1.3 Weight 381g/m2 ± 8.0%
1.4 Water absorbance No more than 0.75g/m2/day
1.5 Heavy Cadmium No more than 0.3 ppm
metal Pb No more than 3.0 ppm
Arsenic No more than 0.1 ppm
Mercury No more than 0.1 ppm

1.6 Limit of microbiological Total aerobic microbial count: ≤190CFU/100cm2

Total yeast and mold count: ≤19CFU/100cm2
Not allowed:
 Escherichia Coli
 Salmonella
 Pseudomonas aeruginosa
 Staphylococcus aureus
PRODUCT STABILITY
(P8)
 STABILITY TEST REPORT
1. Protocol
 Name of product: CETIZYTEC
 Batch No.: 09234NN
 Storage condition: 30 ± 20/710± 5% RH
 Shelf-life: 3 years
2. Testing method:
Criteria When test are Test method Specification
done
Description According to Inspect with Caplet, white color, oval
study process visualization shape, line in the middle,
edges are intact.
Disintegration According to Test performed as per No more than 30 minutes
study process in house specification
and analytical
procedure
Uniformity of According to Test performed as per No less or more than 5%
Weight study process in house specification average weight of caplet
and analytical
procedure
Identification According to Test performed as per Positive for
study process in house specification
and analytical Cetirizine dihydrochloride
procedure
Assay: According to Test performed as per Assay of:
study process in house specification
Cetirizine
and analytical - Cetirizine
dihydrochloride dihydrochloride 90.0 -
procedure
110.0%

compared to the amount

stated on label, count
based on average weight
of one caplet.

3. Result of test
Time Criteria Results
Initial Appearance Passed
Uniformity of volume Passed
Identification Positive
Assay
 Cetirizine dihydrochloride 100.19%
3 months Appearance Passed
Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.17%

9 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.16%

12 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.15%

18 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.14%

24 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.13%

30 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.12%

36 months Appearance Passed

Uniformity of volume Passed
 Identification Positive
Assay
Cetirizine dihydrochloride 100.11%

4. Conclusion
The stability of CETIZYTEC had been tested over 36 months at 30 ± 20C and humidity
710± 5% RH. The result of test shows that the stability of CETIZYTEC can be
guaranteed for 03 years in above storage conditions.
 STABILITY TEST REPORT
1. Protocol
 Name of product: CETIZYTEC
 Batch No.: 09234NN
 Storage condition: 30 ± 20/710± 5% RH
 Shelf-life: 2 years
 Testing method:
Criteria When test are Test method Specification
done
Description According to Inspect with Caplet, white color, oval
study process visualization shape, line in the middle,
edges are intact.
Disintegration According to Test performed as per No more than 30 minutes
study process in house specification
and analytical
procedure
Uniformity of According to Test performed as per No less or more than 5%
Weight study process in house specification average weight of caplet
and analytical
procedure
Identification According to Test performed as per Positive for
study process in house specification
and analytical Cetirizine dihydrochloride
procedure

Assay: According to Test performed as per Assay of:

study process in house specification
Cetirizine
and analytical - Cetirizine
dihydrochloride dihydrochloride 90.0 -
procedure
110.0%

compared to the amount

stated on label, count
based on average weight
of one caplet.

 Result of test
Time Criteria Results
Initial Appearance Passed
Uniformity of volume Passed
 Identification Positive
Assay
Cetirizine dihydrochloride 100.19%

3 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.17%

9 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.16%

12 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.15%

18 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.14%

24 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.13%

30 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
 Cetirizine dihydrochloride 100.12%
36 months Appearance Passed
Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.11%

 Conclusion
The stability of CETIZYTEC had been tested over 36 months at 30 ± 20C and humidity
710± 5% RH. The result of test shows that the stability of CETIZYTEC can be
guaranteed for 03 years in above storage conditions.
 STABILITY TEST REPORT

1. Protocol
 Name of product: CETIZYTEC
 Batch No.: 09234NN
 Storage condition: 30 ± 20/710± 5% RH
 Shelf-life: 3 years
 Testing method:
Criteria When test are Test method Specification
done
Description According to Inspect with Caplet, white color, oval
study process visualization shape, line in the middle,
edges are intact.
Disintegration According to Test performed as per No more than 30 minutes
study process in house specification
and analytical
procedure
Uniformity of According to Test performed as per No less or more than 5%
Weight study process in house specification average weight of caplet
and analytical
procedure
Identification According to Test performed as per Positive for
study process in house specification
and analytical Cetirizine dihydrochloride
procedure

Assay: According to Test performed as per Assay of:

study process in house specification
Cetirizine
and analytical - Cetirizine
dihydrochloride dihydrochloride 90.0 -
procedure
110.0%

compared to the amount

stated on label, count
based on average weight
of one caplet.

 Result of test
Time Criteria Results
Initial Appearance Passed
Uniformity of volume Passed
Identification Positive
 Assay
Cetirizine dihydrochloride 100.19%

3 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.17%

9 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.16%

12 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.15%

18 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.14%

24 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.13%

30 months Appearance Passed

Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.12%

36 months Appearance Passed

 Uniformity of volume Passed
Identification Positive
Assay
Cetirizine dihydrochloride 100.11%

 Conclusion
The stability of CETIZYTEC had been tested over 36 months at 30 ± 20C and humidity
710± 5% RH. The result of test shows that the stability of CETIZYTEC can be
guaranteed for 03 years in above storage conditions.
PRODUCT INTERCHANABILITY
(P9)
Product interchangeability
Not required
 SECTION D:
KEY LITERATURE
REFERENCES
 REFERENCES
Martindale
United State Pharmacopoeia 40 (USP 40)
European Pharmacopoeia 7.0 (EP 7.0)
Vietnam Pharmacopoeia IV
Excipient handbook