Disperse Systems

Liquid preparations containing undissolved or immiscible drug

(dispersed phase) distributed throughout a vehicle (dispersing
phase or dispersion medium)

➢ Suspensions: dispersed phase is a solid that is insoluble in the

vehicle
➢ Emulsions: dispersed phase is a liquid that is immiscible with
the vehicle
➢ Aerosol: dispersed phase is small air bubbles throughout a
solution

1
 Disperse Systems
➢ Particle size of the dispersed phase varies from very large
particles (visible to the naked eye) to very fine ones.
➢ Particles size between 10-50 µm in diameter is usually referred to as
coarse dispersion, e.g. most suspensions and emulsions
➢ Particles 0.5-10 µm is usually referred to as fine dispersion, e.g. gels
➢ Particles 1-500 nm is usually referred to as colloidal dispersion
➢ Coarse dispersions tend to separate more from dispersion
medium than fine particles.
➢ In suspensions: solid particles have density higher than the medium so
they tend to settle to the bottom of the container
➢ In emulsions the oil phase have less density than the aqueous phase
and tend to rise to the top of preparation
➢ For this reason shaking/agitation of the container is necessary in most
dispersion systems
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 Suspensions
➢ A dispersion system of liquid dosage of solid particles (the
suspensoid) are suspended throughout a solvent in which the
drug exhibits minimum solubility.
➢ Because of instability problem, some suspensions may be
prepared as dry-powder for reconstitution

3
 Suspensions
➢ Why suspension?
1. Poor solubility of the drug
2. Chemical Instability of the drug when dissolved
but stability when suspended
3. Overcome unacceptable taste that is difficult to
mask when prepared as a solution even in the
presence of a sweetener and/or flavorant.
➢ E.g. Chloramphenicol has a taste that cannot be
masked in solution but when esterified to
chlorampehicol palmitate (which is insoluble) and
prepared as a suspension, taste is easily masked with a
flavoran (taste buds)
4
 Suspensions
➢ Desired features of suspensions:
1. Settle slowly and readily redisperse upon gentle shaking
2. Particle size should remain constant throughout long
periods of standing
3. Should pour readily and evenly from its container

5
 Suspensions
Sedimentation rate
➢ The rate of settling of particles of suspension.
➢ Stokes’ law:

➢ Ws: rate of settling (m/s)

➢ d: diameter of particles (µm)
➢ Ps: density of particles (g/ml)
➢ P: density of medium (g/ml)
➢ g: gravitational constant (m/s2kg)
➢ µ: viscosity of the medium (Pa.s) (kg/(m.s2)
6
 Suspensions
➢ Stokes’ law is derived for ideal situation:
perfectly spherical particles, very dilute suspension, no
turbulence or collision between particles, no chemical or
physical attraction or affinity to the medium.
This does NOT apply perfectly to pharmaceutical suspensions.
However, Stoke’s law help predict the velocity of
sedimentation.

7
 Suspensions
➢ Points from Stoke’s equation:
➢ As particle size increases, velocity of particles
settling increases
➢ The greater the density of particles, the faster
particles settling
➢ As viscosity of dispersion medium increases, rate
of sedimentation decreases. However, viscosity
has a limit because too viscose liquid cannot pour
➢ Generally, it is easier to modify the dispersed phase rather
than the medium (alter particles….)

8
 Suspensions
Preparation of suspension:

A. Case #1 the drug particles are not penetrated easily by the

vehicle/dispersion medium and tend to clump together or float on
the vehicle, e.g. hydrophobic drugs in water:

Drug particles are first wetted with a solvent like alcohol, glycerol,
propylene glycol, or other hygroscopic solvents. Mixers/blenders
are used to achieve wetting. Those solvents work as wetting agents
by displacing the air in the crevices of the particles which allows
penetration of the dispersion medium (use P&M).

9
 Suspensions
2. All soluble ingredients (flavorant, colorant, preservatives,…)
are dissolved in the dispersion medium

3. Dispersion medium is then added in portions to the wetted

powder and mixed well by the aid of mixers until full
dispersion.

4. A portion of the dispersion medium is used to wash

equipments and to bring suspension to the final volume

5. The final product is then blended well to ensure dispersion

10
 Suspensions
Preparation of suspension:
B. Case #2 the drug particles are easily wetted by the
vehicle/dispersion medium
1. All soluble ingredients (flavorant, colorant,
preservatives,…) are dissolved in the dispersion
medium

2. The drug particles are slowly added to the medium

while mixing to ensure dispersion
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 Suspensions
Preparation of Sustained-Release Suspensions:
It is hard to prepare a sustained release suspension
because it is difficult to maintain stability of
sustained-release particles in a liquid dispersion.

Example:
Pennkinetic systems:
Ionic drug(s) is complexed with ion exchange resins and
the drug-resin complex is coated with ethylcellulose
12
13
 Suspensions, Pennkinetic systems
suspensions
Mechanism of sustainability:

The charged drug is adsorbed onto a resin of opposite

charge

In the gastrointestinal tract ions diffuse into the resin and

displace the drug

The drug slowly leaves the complex through a porous

membrane (ethylcellulose coating)
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 Suspensions
Packaging and storage
➢ Wide mouth containers: ease of pouring and addition of the
vehicle for reconstitution

➢ Adequate airspace above the liquid to permit thorough mixing

by shaking

➢ Tight container

➢ Protect from heat, freezing, and light

➢ Shake well before use

15
 Suspensions
Examples
Antacids Oral Suspension
➢ Drugs to counteract the hyperacidity of the stomach

➢ Most of these drugs are water-insoluble such as aluminum

hydroxide and magnesium hydroxide

➢ Liquid antacids (mainly suspension) are preferred over tablets

because of the more immediate effect in acidity relief

16
 Suspensions, Example
Aluminum hydroxide suspension
Aluminum hydroxide 326.8 g
Sorbitol solution 282.0 ml
Syrup 93.0 ml
Glycerin 25.0 ml
Methyleparaben 0.9 g
Propylparaben 0.3 g
Flavor q.s.
Purified water, to make 1000.0 ml

P.S. Aluminum hydroxide is easily wetted with water, excess amounts may lead to
17
constipation and muscle weakness
 Suspensions, Example
Antibiotics For Oral Suspension
Many antibiotics (Chphenicol, erythromycin, tetracyclines)
are prepared as suspensions and mostly as dry powder
for reconstitution suspensions

Stability, taste, and/or solubility are the main reasons for that

Dry powder contains: antibiotic drug, colorant, flavorant,

sweetener, suspending agent, and preserving agent, …..

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 Suspensions, Example
Antibiotics For Oral Suspension
Examples:

Amoxicillin for Oral Suspension, USP

(Amoxil®)

Cefaclor for Oral Suspension, USP (Ceclor®)

Cefixime for Oral Suspension, USP (Suprax®)

19
 Suspensions, Example
Tips for reconstitution of “for Oral suspension”
➢ Loosen the powder at the bottom of the container by
lightly tapping it against a hard surface

➢ Add purified water, in portions, up to the label-

designated marker and shake well until complete
suspension

20
 Emulsions
An emulsion is a mixture of two immiscible
(unblendable) liquids. One liquid (the dispersed
phase) is dispersed in the other (the continuous
phase).
O/W: oleaginous internal phase and aqueous
external
Dilute it with suitable continuous phase
For a stable emulsion we need an emulsifying
agent.
Depending on constituents, viscosity varies, so
emulsions can be liquids (orally, topically,
parenterally) or semisolids (topically).
They might be classified under other categories
(lotions, creams…etc).

Dr. I. Hamad
Dr. I. Hamad
 Why emulsification?
• Prepare relatively homogenous mixture of 2 immiscible liquids.
• Orally: distasteful oil drug can be administrated in a sweet- flavored
aqueous vehicle.
• Reduced oil particle size makes it more readily absorbed or more
effective.
• In topical preparations; irritant medicinal agents cause less irritation
when in internal phase rather than the continues phase (less contact).
• For topical preparations: using w/o emulsions for treatment of
unbroken skin as it applies evenly on the skin and can wet skin film
(sebum) better. When its necessary to remove emulsion from skin;
this is easier with o/w.
• Again, reduces particle size of internal phase enhances absorption
through skin (precutaneous absorption)

Dr. I. Hamad
 Preparation of emulsions
• Emulsifying agents: (Surfactants) are wetting agents that
lower the surface tension of a liquid, allowing easier
spreading, and lower the interfacial tension between two
liquids. They are amphiphilic, meaning they contain both
hydrophobic groups (their "tails") and hydrophilic groups
(their "heads"). Therefore, they are soluble in both
organic solvents and water. They reduce the interfacial
tension between oil and water by absorbing at the liquid-
liquid interface.
• How to select an emulsifier? Must be compatible with the
other ingredients, must not interfere with the stability or
efficacy of active ingredient, must be stable, non-toxic,
possess little odor, taste or colour.
Dr. I. Hamad
 Theories
• Surface tension theory
• All liquids have a tendency to assume a shape having the minimal surface
area exposed. For a drop of a liquid, that shape is the sphere. A liquid drop
has the shape of a sphere. It possesses internal forces that tend to promote
association of the molecules to resist distortion of the sphere. If two or more
drops of the same liquid come into contact with one another, the tendency is
for them to join or to coalesce, making one larger drop having a smaller
surface area than the total surface area of the individual drops. This
tendency of liquids may be measured quantitatively, and when the
surrounding of the liquid is air, it is referred to as the liquid’s surface tension.
When the liquid is in contact with a second liquid in which it is insoluble and
immiscible, the force causing each liquid to resist breaking up into smaller
particles is called interfacial tension. Substances that reduce this resistance
encourage a liquid to break up into smaller drops or particles. These
tension-lowering substances are surface active (surfactant) or wetting
agents. According to the surface tension theory of emulsification, the use of
these substances as emulsifiers and stabilizers lowers the interfacial
tension of the two immiscible liquids, reducing the repellent force between
the liquids and diminishing each liquid’s attraction for its own molecules.
Thus, the surface-active agents facilitate the breaking up of large globules
into smaller ones, which then have a lesser tendency to reunite or coalesce.
• The oriented-wedge theory assumes monomolecular layers of
emulsifying agent curved around a droplet of the internal phase of the
emulsion. The theory is based on the presumption that certain
emulsifying agents orient themselves about and within a liquid in a
manner reflective of their solubility in that particular liquid. In a system
containing two immiscible liquids, presumably the emulsifying agent is
preferentially soluble in one of the phases and is embedded more
deeply and tenaciously in that phase than the other.
• The plastic or interfacial film theory places the emulsifying agent at the
interface between the oil and water, surrounding the droplets of the
internal phase as a thin layer of film adsorbed on the surface of the
drops. The film prevents contact and coalescing of the dispersed
phase; the tougher and more pliable the film, the greater the stability of
the emulsion. Naturally, enough of the film-forming material must be
available to coat the entire surface of each drop of the internal phase.
A micelle

Dr. I. Hamad
 Types of emulsifiers
• Carbohydrate materials: such as naturally occurring
acacia, tragacanth, agar..etc.
• They form hydrophilic colloids in water producing o/w
emulsions.
• Microcrystalline cellulose is usually used as a viscosity
regulator to retard particle settling and provide dispersion
stability.
• Protein substances: such as gelatin (a colorless water-
soluble glutinous protein obtained from animal tissues
such as bone and skin), egg yolk, casein (a protein
precipitated from milk). These produce o/w emulsions.
Disadv.: produce a very fluid emulsion upon standing.

Dr. I. Hamad
 Types of emulsifiers..cntd.
• High-molecular weight alcohols: such as stearyl alcohol

used as thickening agents and stabilizers for o/w emulsions of lotions and
ointments used externally. Cholesterol derivatives could also be used in
externally used w/o emulsions.
Wetting agents: maybe anionic, cationic or nonionic. (philic and phobic)
lipophilic groups (charged) which account for the surface activity of the
molecule. Depending on their nature, they form either o/w or w/o
emulsions. Anionic like SLS. Cationic like Benzalkonium chloride
(bactericidal activity)
Finely divided solids such as colloidal clays including bentonite, Mg
hydroxide, Al hydroxide. Usually form o/w emulsions.

Dr. I. Hamad
 How to identify emulsion
• Miscibility tests (with oil or water): the emulsion will
only be miscible with liquids miscible with the
continuous phase.
• Conductivity measurements: only emulsions with
aqueous continuous phase will conduct electricity.
• Staining tests: water soluble and oil soluble dyes can be
used and colour the continuous phase

Dr. I. Hamad
 HLB system
• Each emulsifying agent has a hydrophilic and lipophilic
portions (one of them is more predominant)
• Each emulsifying agent has a value according to its HLB
indicating its polarity .
• High numbers (up to 20) indicates a surfactant exhibiting
mainly hydrophilic or polar properties. Low numbers
exhibiting mainly lipophilic or non-polar properties.
• Surfactants with HLB of 3-6 are greatly lipophilic, i.e.,
produce w/o emulsion. Those of 8-18 produce o/w. (See
Tab. 14.2&3)

Dr. I. Hamad
 Methods of emulsion preparation
• Depends on the nature of the components and the
equipment used.
• On small scale (lab or pharmacy) you could use mortar
and pestle, mechanical blender or mixer, a hand or bench-
type homogenizers (See Fig 14.9&10) or in a simple
situation you could use the prescription bottle.
• On large scale: large mixing tanks are used. As desired,
the product can be formed fine by passage through a
colloid mill or through large homogenizer (liquid is
forced under great pressure through an orifice). Industrial
homogenizers can take up to 100,000L/h of product.

Dr. I. Hamad
 Continental or dry gum method
• Its also called 4:2:1 method (4 parts of oil, 2 water and 1 gum to
prepare the primary emulsion). E.g., if 40 ml of oil to be emulsified:
use 20 ml of water and 10 gm of gum. Additional water and
ingredients added afterward.
• In this method: acacia (or o/w emulsifier) is triturated with the oil in
a rough-inner surface dry mortar, then the 2 parts of water are added
at once and the mixture is triturated and mixed rapidly until
producing the white creamy primary emulsion (about 3 minutes).
Other materials are mixed with continuous phase and added later on.
Substances that might interfere with the stability of the gum or oily
phase are added at last with continuous phase (alcohols precipitates
gum so should not be added during primary). When all agents are
added, then transfer into a graduate and made to volume with water
swirled in the mortar.
• In some cases, the amount of acacia should be adjusted upward (in
mineral oil requires 3:2:1).
• Pharmacist can use electric mixer or blinder instead of mortar.

Dr. I. Hamad
 English or wet gum method
• Same proportion used previously but can be changed
during the preparation as seen necessary by the operator,
also the mixing is different.
• Mucilage of gum is prepared by triturating granular
acacia with twice its weight of water. The oil is then
added slowly in portions and the mixture is triturated to
emulsify the oil. If the mixture becomes too thick, more
water should be added before adding additional oil. After
adding all portions of oil, extra mixing should be applied
to ensure uniformity. The rest of the preparation is same
as in the continental method.

Dr. I. Hamad
 Bottle method
• This method is useful to prepare emulsions from volatile
oils or low oleaginous substances of low viscosities.
• Powdered acacia is placed in a dry bottle, 2 portions of oil
are added, thoroughly shaken in a capped container.
Equal amount of water (to oil) is added and continuous
shaking. After complete amount of water is added, the
primary emulsion formed is then diluted to the proper
volume with water or the aqueous solution of other
formulative agents.
• This is not suitable for viscous oil coz they are hard to be
agitated in a bottle with the emulsifying agent.
• When the oil phase is mixture of fixed oil and volatile
oil, then the dry gum method is preferred.

Dr. I. Hamad
 Auxiliary methods
• Increasing the quality of dry or wet gum prepared
emulsions can be achieved by passing it through a hand
homogenizer.
• The pumping handle forces the emulsion through a very
small orifice that reduce the globules size of the internal
phase to about less than 5 µm.
• Its not very efficient in reducing size of highly viscous
(very thick) emulsions.
• should not be used for emulsions containing high
proportion of solid matter.

Dr. I. Hamad
 In situ soap method
• Calcium soaps are w/o emulsions that contain certain
vegetable oils such as oleic acid in combination with
limewater (USP: Calcium Hydroxide solution).
• Preparation: mix equal amounts of oil and limewater.
• The emulsifying agent here is the Calcium salt of the free fatty
acid formed from the combination of the oil and limewater
(the free fatty acid is oleic acid so the emulsifying agent is Ca
oleate).
• Sometimes the amount of free fatty acids in the oil are
insufficient in 1:1 basis with Ca(OH)2. either add extra oil or
small amount of oleic acid (to avoid tiny water droplets
forming on the surface)
• As the oil phase is the external phase, this is used for skin
softening, such as itchy skin.
Dr. I. Hamad
 Microemulsions
• Emulsions with particle size of micrometers which are
thermodynamically stable and transparent stabilized with
the right choice of surfactant.
• Surfactants with HLB values of 15-18 are heavily used to
formulate o/w microem. (surfactants-Tween 60&80- are
said to solubilize the oil, but still they are dispersed
phase).
• Adv.: more rapid and efficient oral absorption of drugs
than solid dosage forms, increased diffusion through skin
in transdermal routes, used in development of artificial
RBC’s and targeting of cytotoxic drugs to cancer cells.

Dr. I. Hamad
 Stability of emulsions
• Emulsion is said to be physically unstable if: internal phase forming
globules or aggregates upon standing, large globules rise to top or
fall to the bottom, and if all or part of internal phase separates.
Moreover, microbial contamination might occur.
• Aggregation and coalescence: aggregates of globules tend to either
rise to top or fall to bottom more than individual globules, this
termed creaming of emulsion. It’s a reversible process if
coalescence is absent. Otherwise, improper dosing is a problem.
• According to Stoke’s law: rate of separation is increased with the
increase of particle size of the internal phase, larger density
difference between the 2 phases and low viscosity external phase.
• Thickeners (tragacanth) are used to increase viscosity.
• Downward or upward creaming take place due to lesser or higher
density of the internal phase.

Dr. I. Hamad
 Stability of emulsions.. Cntd.
• More problematic is coalescence of the globules into a separate
layer. Its termed breaking and it’s irreversible because the
protective sheath doesn’t exist anymore. Usually reagitation is
useless, so additional emulgent and reprocessing in suitable
machinery are required.
• Generally, protect emulsion against excessive heat and cold.
Freezing or thawing or even extra-heating roughen the emulsion
and might break it. To determine stability, tests are done on 5, 40
oC (for 3 months) and 50 oC (for relatively shorter periods).

• Appropriate formulating and packaging steps should be taken in

consideration to minimize the effect of light, air and
contaminating microorganisms (amber light, antioxidants,
alcohol acts as a good preservative against fungi in % of 12-15
for oral w/o emulsions)

Dr. I. Hamad
 Preservation of emulsions
• Methods of testing preservatives activity essentially involve
the addition to the test products of a mixture of Gram-positive
and Gram-negative bacteria, yeasts and moulds.
• Preservation from microorganisms:
• It is necessary to preserve the emulsions from microorganisms
as these can proliferate easily in emulsified systems with high
water content, particularly if carbohydrates, proteins or
steroidal materials are also present.
• Contamination due to microorganisms can result in problems
such as color and odor change, gas production, hydrolysis, pH
change and eventually breaking of emulsion. Therefore is
necessary that emulsified systems be adequately preserved.

Dr. I. Hamad
 Preservation of emulsions..cntd.
• An ideal preservative should be nonirritant and nontoxic
in the concentration used. It should be physically as well
as chemically compatible with other ingredients of the
emulsions and with the proposed container of the product.
• It should not impart any taste, color or odor to the
product. It should be stable and effective over a wide
range of pH and temperature.
• It should be stable and effective over a wide range of pH
and temperature. It should have a wide spectrum of
activity against a range of bacteria, yeasts and moulds.
• It should have bactericidal rather than bacteriostatic
activity.

Dr. I. Hamad
 Preservation of emulsions..cntd.
• Examples of antimicrobial preservatives used to preserve
emulsified systems include parahydroxybenzoate esters
such as methyl, propyl and butyl parabens, organic acids
such as ascorbic acid and benzoic acid, organic mercurials
such as phenylmercuric acetate and phenylmercuric
nitrate, quarternary ammonium compounds such as
cetrimide, cresol derivatives such as chlorocresol and
miscellaneous agents such as sodium benzoate,
chloroform and phenoxyethanol.

Dr. I. Hamad
 Preservation from oxidation
• Oxidative changes such as rancidity and spoilage due to
atmospheric oxygen and effects of enzymes produced by
micro-organisms is seen in many emulsions containing
vegetables and mineral oils and animal fats. Antioxidants
can be used to prevent the changes occurring due to
atmospheric oxygen.
• Antioxidants are agents having a high affinity for oxygen
and compete for it with labile substances in the
formulation. The ideal antioxidant should be nontoxic,
nonirritant, effective at low concentration under the
expected conditions of storage and use, soluble in the
medium and stable. Antioxidants for use in oral
preparation should also be odorless and tasteless.

Dr. I. Hamad
 Preservation from oxidation..cntd.
• Some of the commonly used antixidants for emulsified
systems include alkyl gallate such as ethyl, propyl or
dodecyl gallate, butylated hydroxyanisole (BHA),
butylated hydroxytoluene (BHT)

Dr. I. Hamad
 Ointments
• Semisolid, greasy preparation (usually containing a
medicine) applied externally as a remedy or for soothing
an irritation.
• Ointment bases: oleaginous bases, absorption bases,
water-removable bases and water soluble bases.
• Oleaginous bases: (hydrocarbon bases): have emollient
effect, protect against escape of moisture, remain on skin
for long periods before drying out, difficult to wash off
(immiscible with water), water and aqueous preparations
can be added in small amounts.
• Examples: petrolatum, white petrolatum, white ointment
ad yellow ointment.

Dr. I. Hamad
 Examples of hydrocarbon bases
• Petrolatum: Vaseline, is a mixture of semisolid hydrocarbons
obtained from petroleum (with carbon numbers mainly higher
than 25). It’s smooth slippery mass, varying in colour from
yellowish to light amber. Melts at 38-60 oC. Also known as
yellow petrolatum or petrolatum jelly.
• White petrolatum: white Vaseline, from petrolatum that has
been wholly or nearly decolorized. Because of its light colour
it is preferred by some pharmacists and patients. Also known
as white petrolatum jelly.
• Yellow ointment: (it’s a 50g of yellow wax + 950g of
petrolatum) yellow wax is the purified wax obtained from the
honeycomb of the bee Apis mellifera. Melt the yellow wax on
water bath then add the petrolatum until the mixture is
uniform, cool and stir until solidify.it has slightly greater
viscosity than plain petrolatum, also called simple ointment.
Dr. I. Hamad
 Examples of hydrocarbon bases..cntd.
• White ointment: only change into white wax (bleached
and purified yellow wax) and white petrolatum.

Dr. I. Hamad
 Absorption bases
• There are 2 types:
• A) Those permit the incorporation of aqueous solutions
resulting in the formation of w/o emulsions (e.g., hydrophilic
petrolatum)
• B) Those that are w/o emulsions (emulsion bases) that permit
the incorporation of additional quantities of aqueous solution (
e.g., Lanolin).
• These bases are used as emollients and not easily removed
from the skin with water washing.
• Absorption bases are used to incorporate small volume of
aqueous solution into hydrocarbon bases (i.e.: incorporating
the aqueous solution into the absorption base and then
incorporating the mixture into the hydrocarbon base.

Dr. I. Hamad
 Hydrophilic Petrolatum
• Has the following formula ( 30g of Cholesterol + 30g of
stearyl alcohol + 80g of white wax + 860g of white
petrolatum)
• Melt the stearyl alcohol and the white wax in steam bath,
then add the cholesterol with stirring until dissolved, then
add the white petrolatum, allow the mixture to cool while
stirring until congealed.
• Example: Aquaphore: has the capacity to absorbs up to
three times its weight in water.

Dr. I. Hamad
 Lanolin
• Obtained from the wool of sheep, is a purified wax like
substance that is cleaned, deodorized, decolourized. It
contains not more than 0.25% water.
• Additional water can be incorporated into lanolin by
mixing.
• Modified lanolin is lanolin that has been processed to
reduce the contents of free lanolin alcohols and any
detergents residues. Those are less sensitizing than
normal lanolins

Dr. I. Hamad
 Water-removable bases
• Are o/w emulsions resembling creams easily washed
from skin, often called water-washable bases. They
maybe diluted with water or aqueous solutions
• E.g., hydrophilic ointment: following formula (0.25g of
methylparaben+ 0.15g of propylparaben (both
antimicrobial preservatives) + 10g of SLS (emulsifier) +
120g of propylene glycol+ 250g of stearyl alcohol (oil
phase)+ 250g of white petrolatum (oil phase) + 370g of
purified water).
• The 2 oily components are melted together at around 75
oC. Dissolve other ingredients in the purified water and

add with stirring until the mixture congeal.

Dr. I. Hamad
 Water-soluble bases
• Don’t contain oleaginous components. Greaseless and
totally water washable, they are used for incorporation of
solid substances.
• The polyethylene glycol polymers are of great importance
in ointments. PEG [CH2-CH2-O]n, is a polymer of ethylene
oxide C2H4O and water. The names of PEG’s include
numbers that roughly indicate their average molecular
weight. PEG’s with MWts in the area of 1,000 are soft,
ointment-like substances. As the molecular weight
increases, they become harder and they finally become
waxes. They are water-soluble, nonvolatile, and do not
deteriorate or support mold growth.
Dr. I. Hamad
 Water-soluble bases..cntd.
• Formulations.
• (a) The most suitable PEG ointment bases are
formulations of heavy (3350, solid) and light (400, liquid)
molecular-weight PEG, such as the formula below results
in a very pliable semisolid ointment.
• Polyethylene Glycol Ointment, USP:
Polyethylene Glycol 3350 40%
Polyethylene Glycol 400 60%

Dr. I. Hamad
 Water-soluble bases..cntd.
• The previous base is so water-soluble that not more than 5
percent water can be added in making ointments. When
greater volumes of water must be added to the ointment,
the following formulation is recommended:
• Polyethylene Glycol 4,000 47.5%
• Polyethylene Glycol 400 47.5%
• Stearyl Alcohol 5.0%

Dr. I. Hamad
 Water-soluble bases..cntd.
• Summary of water-soluble bases. We can sum up the
important aspects of the water-soluble ointment bases as
follows:
• (a) Properties. Anhydrous, but will absorb water and
dissolve in water; washable; nongreasy.
• (b) Examples. Carbowax compounds such as the
polyethylene glycol ointment already mentioned
(c) Advantages. Wide range of compatibility; do not
become rancid or support microbial growth; nonirritating
(to the same degree as lanolin, petrolatum, etc); adhere
well to skin; easily washed off; low incidence of
sensitization
• (d) Disadvantages. Sometimes undergo gradual
discoloration with certain drugs. Unless stearyl alcohol is
added, an aqueous solution can be added only to the
extent of 5 percent

Dr. I. Hamad
 Selection of the right base
• Take care of the following:
• Desired release rate of the drug from the ointment base
• Desirability of topical or percutaneous drug absorption.
• Desirability of occlusion of moisture from the skin.
• Stability of the drug in the ointment base.
• Effect of the drug on the consistency of the base
• Desire for easily water-removable base.
• Characteristics of the surface to which it is applied.
• Generally, ointment is applied to dry, scaly skin, while
creams is applied to weeping or oozing surfaces. Lotions
are applied to areas where friction is frequent (between
thighs or under armpit.

Dr. I. Hamad
 Preparation of ointments
• Incorporation method: components are mixed to attain a
uniform preparation, see Fig 10.1. for large scale
production.
• On small scale production, pharmacist can mix up the
components in a pestle and mortar, spatula can be used to
rub the components together on an ointment slab (tile; An
ointment slab is a heavy piece of glass with a rough
surface on one side to help reduce the size of solid
particles) which might be covered with a non-absorbent
paper.

Dr. I. Hamad
 Incorporation of solids
• By spatulation, use a wide stainless steel spatula with a smaller
one to remove big bulks (use rubber spatula if the metal reacts to
other components). Start thoroughly rubbing the components
together until smooth and uniform. Previously reduce powders
particle size on the side of the slab and the base on the other side,
mix small portion of powder with a portion of base until
uniform.. continue mixing.
• Lavigation: reducing powder particle size by dispersing it in a
vehicle in which it’s insoluble (like mineral oil in w/o, glycerin
for o/w). Lavigating agent is equal in volume to the solid (use
pestle&mortar). After lavigation, introduce the dispersion to
base.
• Water soluble solids are dissolved in water before addition to
base (use pestle&M for large amounts of liquids).
• For gummy material (Camphor); pulverization is used, the
material is dissolved in a solvent and spread it on the tile. The
solvent evaporates leaving a thin layer on which other ingredients
are added by trituration with a spatula.
Dr. I. Hamad
 Incorporation of liquids
• How much water the base can contain?
• Small amounts of alcoholic solutions can be added easily
to oleaginous bases (natural Balsams, usually mixed with
equal amounts of castor oil before incorporating into
base)
• Ointment or roller mills are used to obtain ointments
which are uniform in composition and smooth in texture.
Small lab mills can be used too.

Dr. I. Hamad
Dr. I. Hamad
 Fusion Method
• The fusion method is particularly useful when solid waxes are
included in the ointment to add viscosity. In this method, first
melt the substance with the highest melting point by using a
water bath, but use as little heat as necessary. Then add the
other ingredients on the basis of their decreasing melting
points. When the entire mixture is liquefied, remove it from
the water bath. Then stir the mixture until it congeals, to
prevent possible separation and crystallization. On a small
scale, use a porcelain dish or a glass beaker. On a large scale,
its carried out using large steam-jacketed kettles. Once
congealed, pass emulsion through a mill or easily rub it with a
spatula or use a pestle&M.
• Preparation of emulsion-base ointments: this involves both
melting and emulsification. Melt the wax and oil components.
Heat water soluble materials in water to same temperature
(solidification of oils), then add the aqueous solution slowly.

Dr. I. Hamad
 Ointments requirements
• Ointments should meet USP tests for: microbial content,
minimum fill, packaging storage and labeling.
• Microbial content: ointments are not necessarily sterile (unless
ophthalmic). Certain susceptible ointments should contain
preservatives (methyl & propyl parabens, phenols, benzoic acid,
ascorbic acid, and quaternary ammonium salts).
• USP requires the absence of certain microbes from ointments
(like betamethasone valerate ointment); Staphylococcus aureous
and pseudomonas aeruginosa because of their capacity to infect
the skin.
• USP requires sticking to environmental control and application of
GMP to minimize type and number of microbes; this involves
testing of raw materials, use of acceptable water, in-process
control, and final product testing.
• Tests for yeasts and molds for rectal urethral and vaginal
ointments should also be carried out

Dr. I. Hamad
 DISPENSING OINTMENTS
• Ointments are traditionally packaged in jars and collapsible
tubes. The jars are made of glass that is either green or opaque
white. Ordinary tin tubes are convenient to the patient because
they are easier to carry and do not break when they are
dropped. They are especially valuable for ointments that lose
moisture or decompose on exposure to the atmosphere.
• Filling Ointment Jars. Ointment jars, available in many sizes
ranging from
• 1/4 ounce to a pound and larger, may be filled by packing the
ointment into them with a small spatula. In packing, the sides
and bottom all the way around should be covered first, adding
the final portions to the center and top in order to minimize air
pockets.
• Melted ointments containing no material likely to settle out
may be poured into containers while still warm and fluid. In
either case, the ointment should be smoothed off at the top
before the lid is closed
Dr. I. Hamad
• Filling Ointment Tubes: You can fill ointment tubes at the
pharmacy by first rolling the ointment into a glassine powder
paper to make a cylinder just smaller than the base of the tube.
Remove the cap of the tube so that air will not be trapped when
the ointment is inserted. Insert the roll, ointment and paper
combined, as far into the tube as the roll will go and close it by
carefully flattening the end of the tube. Hold the end of the tube
closed with firm pressure from the side of a spatula and carefully
pull the glassine paper out of the tube. The ointment is left in the
tube. Fold the end of the tube over twice, crease it tightly, and
score it several times with the spatula edge to prevent it from
opening during use.
• Labeling: Select a label corresponding in size to the size of the
jar being used. Metal ointment tubes should be moistened with
tincture of benzoin before the label is applied to help the label
adhere. When the label has been put into place, it should be
covered with a strip of cellophane tape. The auxiliary label "For
External Use Only" is required on all ointments, pastes, and
creams
• Additional standards: viscosity studies, in-vitro drug release (to
ensure uniformity)

Dr. I. Hamad
 Gels
• Semisolid systems consisting of dispersions made up of either small
inorganic particles or large organic molecules interpenetrated by a
liquid. The particles link together to form an interlaced network;
imparting a rigidity to the structure. Often, a small % of disperse
phase is needed to impart rigidity (e.g., 1% of Agar in water
produces a firm gel). A gel rich in liquid may be called a jelly, if the
liquid is removed and only the gel framework remains this is termed
Xerogels.
• Gels where macromolecules are distributed so that no apparent
boundaries between them and the liquid are called single-phase gels.
When the gel consists of floccules of small and distinct particles,
two-phase gels.
• Sol: general term for dispersions of solid substances in a liquid, solid
or gas medium; hydrosol (water medium) alcosol (alcohol medium).
Aerosol is dispersion of solid or liquid in gas.

Dr. I. Hamad
 Cationic polymers
• Are positively charged polymers. Their positive charges
prevent the formation of coiled polymers. This allows
them to contribute more to viscosity in their stretched
state, because the stretched-out polymer takes up more
space than a coiled polymer and this resists the flow of
solvent molecules around it. Cationic polymers are a main
functional component of hair gel, because the positive
charged polymers also bind the negatively charged amino
acids on the surface of the keratin molecules in the hair.
More complicated polymer formulas exist, e.g., a
copolymer of vinylpyrrolidone

Dr. I. Hamad
 Types of gels
• Hydrogel (also called Aquagel) is a network
of polymer chains that are water-insoluble,
sometimes found as a colloidal gel in which
water is the dispersion medium. Hydrogels are
super absorbent (they can contain over 99%
water) natural or synthetic polymers.
Hydrogels also possess a degree of flexibility
very similar to natural tissue, due to their
significant water content.

Dr. I. Hamad
• Common uses for hydrogels include
• currently used as scaffolds in tissue engineering. When
used as scaffolds, hydrogels may contain human cells in
order to repair tissue.
• environmentally sensitive hydrogels. These hydrogels
have the ability to sense changes of pH, temperature, or
the concentration of metabolite and release their load as
result of such a change.
• as sustained-release delivery systems
• provide absorption capacities of necrotics and fibrotic
tissue.
• used in disposable diapers where they "capture" urine,
or in napkins
• Contact lenses (silicone hydrogels, polyacrylamids)

Dr. I. Hamad
• Other, less common uses include
• Breast implants
• dressings for healing of burn or other hard-to-heal
wounds. Wound gels are excellent for helping to create
or maintain a moist environment.
• reservoirs in topical drug delivery
• Common ingredients are e.g. polyvinyl alcohol, sodium
polyacrylate, acrylate polymers and copolymers with an
abundance of hydrophilic groups.
• Natural hydrogel materials are being investigated for
tissue engineering, these materials include agarose,
methylcellulose, hylaronan, and other naturally derived
polymers.

Dr. I. Hamad
 Organogels
• An organogel is a non-crystalline thermoreversible
(thermoplastic) solid material composed of a liquid
organic phase entrapped in a three-dimensionally cross-
linked network. The liquid can be e.g. an organic solvent,
a mineral oil or a vegetable oil. The solubility and particle
dimensions of the structurant are important characteristics
for the elastic properties and firmness of the organogel.
Often, these systems are based on self-assembly of the
structurant molecules.
• Organogels have potential for use in a number of
applications, such as in pharmaceuticals, cosmetics, art
conservation, and food. An example of formation of an
undesired thermoreversible network is the occurrence of
wax crystallization in crude oil.
Dr. I. Hamad
 Xerogels
• A xerogel is a solid formed from a gel by drying with
unhindered shrinkage. Xerogels usually retain high
porosity (25%) and enormous surface area (150–900
m2/g), along with very small pore size (1-10 nm).
When solvent removal occurs under certain
conditions, the network does not shrink and a highly
porous, low-density material known as an aerogel is
produced. Heat treatment of a xerogel at elevated
temperature produces viscous (shrinkage of the
xerogel due to a small amount of viscous flow) and
effectively transforms the porous gel into a dense
glass.

Dr. I. Hamad
• Because of the high degree of attraction between
the disperse phase and the aqueous medium in
gels, these preparations remain fairly uniform on
standing, with little settling of the disperse
phase. However, on long standing, a supernatant
layer of the dispersion medium might develop,
but the uniformity of the preparation is easily
reestablished by moderate shaking. To ensure
uniform dosage, gels should be shaken before
use, and a statement to that effect must be
included on the label of such preparation.

Dr. I. Hamad
 Creams
• Are semisolid preparations containing one or more
medicinal agents dissolved or dispersed in either O/W or
W/O emulsions or in water washable pastes.
• Oil-in-water creams are more comfortable and
cosmetically acceptable as they are less greasy and more
easily washed off using water. Water-in-oil creams are
more difficult to handle but many drugs which are
incorporated into creams are hydrophobic and will be
released more readily from a water-in-oil cream than an
oil-in-water cream. Water-in-oil creams are also more
moisturizing as they provide an oily barrier which reduces
water loss from the stratum corneum, the outmost layer of
the skin.
Dr. I. Hamad
 Uses of creams
• The provision of a barrier to protect the skin
– This may be a physical barrier or a chemical
barrier as with sunscreens
• To aid in the retention of moisture
• Cleansing
• Emollient effects
• As a vehicle for drug substances such as local
anaesthetics, anti-inflammatories, (NSAIDs or
corticosteroids), hormones, antibiotics, antifungals, or
counter-irritants

Dr. I. Hamad
 Medical uses
• Creams without medication can be used on skin conditions like psoriasis
and eczema that require a moisture barrier and maximal moisturizing. Even
those with only very dry skin would benefit from the use of unmedicated
cream.
• Hydrocortisone cream is available to treat rashesand also helps those with
other skin conditions such as psoriasis and eczema. Antibiotic creams can
be used on abrasions or small wounds to prevent or treat minor infections.
Antifungal creams are used in those with patches of fungal infections, such
as ringworm, Candida diaper rash. Zinc oxide cream is used for local
sunblock activity and for infant diaper rash.
• More recently, a cream called Emla was developed. Emla contains the
drug, lidocaine, and is placed on intact skin for several minutes prior to
starting an intravenous line or drawing blood in those people, like children,
who don’t tolerate the pain of needle sticks.
• Compounding pharmacists can make creams with hormones such as
estrogen, progesterone and testosterone in them. Patients put a small
amount of cream on the inside of their forearm or upper arm and rub the
cream into the skin. This has been shown to be as effective (or more
effective) than providing these hormones in oral form

Dr. I. Hamad
• This term creams has traditionally been applied to
semisolids that possess a relatively fluid consistency
formulated as either water-in-oil (e.g., Cold Cream)
or oil-in-water (e.g., Fluocinolone Acetonide Cream)
emulsions. However, more recently the term has been
restricted to products consisting of oil-in-water
emulsions or aqueous microcrystalline dispersions of
long-chain fatty acids or alcohols that are water
washable and more cosmetically and aesthetically
acceptable. Creams can be used for administering
drugs via the vaginal route (e.g., Triple Sulfa Vaginal
Cream).

Dr. I. Hamad
 Creams vs ointments
➢ Creams are less oily (less greasy) and viscous than ointment

➢ Creams spread easier and faster than ointments, can be used on

larger skin areas

➢ Easier to remove than ointments

➢ Water evaporates faster than that in ointments, this gives a cooling

sensation

➢ Creams are absorbed faster

➢ Creams can be used on oozing skin

➢ Less stiff than ointments

➢ Good appealing/cosmetic prosperities compared to ointments

• Examples of commonly used creams:

➢ Vanishing creams

➢ o/w emulsions containing large proportion of water and stearic acid

➢ When applied to the skin there is little or no presence of the cream

➢ After application, water evaporates and leaves a thin (almost

undetectable) film of stearic acid

➢ Used as a moisturizer to the skin

➢ Used for both oily and dry skin

➢ Used before make-up to give glow to the face

• Examples of commonly used creams:

➢Cold creams
➢w/o emulsions of beeswax

➢Emollient

➢Cleansing cream, used to remove make up

➢It gives a cooling feeling when applied to the skin

 Pastes
• Semisolid preparations (ointment-like) intended for application to the skin.

➢ They are ointments of finely dispersed solid but with very large proportions
of solid materials

➢ Solids may make ~ 25-60% w/w

➢ Prepared by same methods for ointments (incorporation or fusion)

➢ When a levigation is required, the same ointment base is used as a

levigating agent rather using a solvent

➢ Large proportions of solids result in

➢ High degree of stiffness and thicker which helps the product to remain
in place of application

➢ Free of gritty particles

➢ Large proportions of solids result in

➢ Absorbs skin secretions, more absorptive than ointments

➢ Opaque

➢ Very viscous

➢ Adhere very well to the skin, protective layer

➢ Highly impermeable

➢ Not suitable for application on hairy skin

➢ Few pastes are commercially available, e.g.

➢ Zinc oxide paste

➢ Zinc oxide and salicylic acid paste

 Aerosols
• Technically, an aerosol (pressurized package) is a suspension
of fine solid particles or liquid droplets in a gas. They depend
on the function of the container, its valve assembly, and its
added component (propellant)
• Pressure is applied to aerosols through using liquefied or
gaseous propellant.
• Contents are expelled as fine mist, coarse, wet, or dry spray;
steady stream; or stable fast-breaking foam depending on use.
• Aerosols for inhalation therapy (asthma or emphysema) must
be fine liquid mist or very fine solid particles: less than 6 µm
reach bronchioles, less than 2 reach alveolar ducts and alveoli
(See Fig. 14.11). Aerosols for dermatologic spray are coarser
(foams as powder, wet spray like local anesthetic). Others
include vaginal and rectal foams.

Dr. I. Hamad
 Adv. Of aerosols
• Only a small portion of the medicament easily withdrawn
without exposure of remaining material.
• Protect drugs inside (oxygen, moisture, light, sterile)
• Topical easily administrated (uniform thin layer) with no
touching. Also cooling and refreshing effect.
• Dosage and particle size can be controlled by proper
formulation and valve control
• It is a clean process requires little or no wash-up

Dr. I. Hamad
 Aerosol principle
• Aerosol consists of 2 component parts: product concentrate
(active+additives) and the propellant (if its liquefied gas it also
serves as the solvent or vehicle): compressed gases CO2, nitrogen,
nitrous oxide (N2O) are employed as propellant.
• Chlorofluorocarbons were the most propellant used but now
prohibited for nonessential use (ozone and UV)
• Fluorinated hydrocarbons are gases at RT, could be liquefied by
cooling below their boiling P or by compression at RT (Feron 12
forms a liquid when when cooled to -30 C or when compressed to
70 psig at 21 C.
• When the propellant packed into the aerosol, portion of the liquefied
gas stay liquid and some vaporizes to occupy the upper part
(equilibrium) (see Fig.14.12). The vapor phase exerts pressure
inside in all directions that causes liquefied with the concentrate to
be released. Once the propellant meets the air, it expands and
evaporates (drop in pressure) leaving the concentrate. The liquid-gas
equilibrium is then reestablished.

Dr. I. Hamad
 Aerosol systems
• Pressure inside aerosol is critical and controlled by: type and
amount of propellant and nature of concentrate. So it’s not
possible to generalize
• General statement: space sprays contain greater proportion of
propellant (released with greater pressure from the valve: 30-40
psig at 21 C ~ 85% propellant). Surface aerosols (for surface
coating) commonly contain 25-55 psig at 21 C ~ 30-70%
propellant. While foam aerosols operate at 35-55 psig at 21 C ~
6-10% propellant.
• Foam aerosols maybe considered to be emulsions: liquefied
propellant is partially emulsified with the product concentrate not
dissolved in it (fluorinated hydrocarbons are non polar organic
solvents and will not dissolve in the aqueous formulation),
surfactants could be used. Shake to mix propellant with
concentrate
Dr. I. Hamad
 Aerosol systems..cntd.
• Mixtures of propellants are used to provide desired vapor
pressure and proper solvent features.
• Some propellants are excluded (they may interact with the
concentrate or aerosol system): CCl3F forms free HCl with
water or ethyl alcohol (commonly used cosolvents) that affects
the efficacy of the product and furthermore corrodes container.
• Physiologic effect of the propellant should be considered:
combination of propellants might give undesired effect
(although individually not)
• fluorinated hydrocarbons are low toxic, although
some individuals might be sensitive and develop
cardiotoxic effect.

Dr. I. Hamad
 Mode of Operation
Liquefied-gas systems

▪ After sealing the canister,

the liquefied gas immediately separates

into a liquid and vapor phases

▪ After molecules enter the vapor state

a pressure gradually develops

▪ The more molecules in the vapor

Phase the higher the pressure

This pressure is sufficient to push the

liquefied gas up the dip tube and against the valve

68
 Aerosol systems..cntd.
• Two-phase system: as discussed contains liquid phase with the concentrate
plus the vapor phase.
• Three-phase system: consists of a layer of water immiscible liquid
propellant (higher density) a layer of highly aqueous concentrate (water)
and the vapor phase. Upon activation; the dip tube must only reach within
the concentrate aqueous phase and not down to the liquefied propellant.
• Compressed gas systems: compressed rather than liquefied. Compressed
gases present in the space above liquid-product concentrate. Pressure here
forces liquid concentrate up the dip tube and out the valve. Use of gases
which are insoluble in the product concentrate (nitrogen) will release
concentrate as it is. Nitrogen is inert and provide protection against
oxidation plus its odorless and colourless gas.
• Carbon dioxide and nitrous dioxide are slightly soluble in the liquid
concentrate phase but used when expulsion with the concentrate is needed
to achieve spraying or foaming.
• These compressed gas systems have no propellant or reservoir so high
pressure is needed to start with (no compensation) and this pressure
disappears when product is used

Dr. I. Hamad
 optimal
airway
deposition

Dr. I. Hamad
 Aerosol container and valve assembly
• Containers: various materials: glass (uncoated or plastic coated);
metal (like tin-plated steel), aluminum and stainless steel; and
plastic.
• Should be adaptable to production method, compatible with
formulation components, ability to sustain the pressure intended for
the product, the interest in design and cost.
• Glass: although brittle and fragile, preferred for most aerosols:
chemical compatibility, not subject to corrosion, and more adaptive
to creativity in design. Glass containers must be safely pressurized.
Plastic coating is applied to prevent breakage. Glass containers are
considered safe when the pressure is below 25 psig and not more
than 50% propellant.
• Tin-plated steel is the most commonly used metal containers. When
required, special coating might be applied between the container and
the contents.
• Aluminum containers have Adv.: greater safety against leakage,
more compatible and less corrosion.
• Plastic containers: problems with penetration of vapor within the
container, and drug-plastic interaction.
Dr. I. Hamad
 Valve assembly
• The function is to allow expulsion of the contents of the can in the
desired form and rate and proper amount (metered). Materials used
in the manufacture: plastic, rubber, aluminum and stainless steel.
• Actuator: the pressing button. The product is discharged through its
orifice (contributes to the form; mist, solid stream, foam..etc.)
• Stem: supports the actuator
• Gasket: prevents leakage of formulation when the valve is closed.
• Spring: by which actuator retracts when pressure is released
• Mounting cup: holds the valve in place.
• Housing: links the dip tube, stem and actuator. Its orifice determines
the delivery rate and form.
• Dip tube : from housing down to the product, inner dimension is
important.

Dr. I. Hamad
Dr. I. Hamad
 Metered dose inhalers MDIs
• When the formulation is potent medication. The amount
of material discharged is regulated by an auxiliary valve
chamber. A single depression of the actuator causes
evacuation of this chamber and delivery of its content.
• Particle size plays important role in delivering
medication, breathing patterns and depth of respiration as
well.

Dr. I. Hamad
Steps for using an MDI

1. Remove the cap from the inhaler

2. Shake the inhaler

3. Breathe out as much air as you can

4. Put the mouthpiece of the inhaler into your mouth (keep your tongue under the inhaler)
and close your lips tight

5. Trigger the inhaler at the very beginning of a long, slow, deep breath. The inhaler triggers
when you press the canister down into the plastic holder

6. Hold your breath for 10 seconds or to the count of 10

7. If you are using a bronchodilator, wait 1-2 minutes between puffs

8. Repeat until you have taken the prescribed number of puffs

9. Clean the plastic holder once a week by removing the canister from the holder and running
warm water through it for 30 seconds. Twist the canister back into place after the holder
has air dried
MDIs

Dr. I. Hamad
 Filling operations
• Cold filling: concentrate and propellant must be cooled to 34.5-40 C. this
liquefies the propellant gas. The cooling system may be a mixture of dry
ice and acetone or refrigeration systems. Liquefied gas is added to the
chilled concentrate in cold aerosol container. The heavy vapors of the cold
liquid propellant displace the air in the container. When propellant is
added, the valve assembly is inserted and crimped into place.
• Aqueous systems cannot be filled by this process (very low temperature
may turn water to ice).
• Pressure filling: concentrate is placed in the aerosol, valve assembly is
inserted and crimped into place, and the liquefied gas under pressure is
metered into the valve stem from a pressure burette. After filling, the
actuator is tested for proper function.
• Pressure felling is used for most pharmaceutical aerosols. Adv over cold
felling: less danger of moisture contamination and less propellant lost in the
process.
• When compressed gases is used as propellant: same procedure but air is
evacuated by a vacuum.

Dr. I. Hamad
 Testing the filled container
• Tested under various environmental conditions for leaks
or weakness in the valve assembly or container. The valve
discharge rate is also determined . Aerosols are tested for
their spray patterns, particle distribution, and for accuracy
and reproducibility of dosage when using metered valves.

Dr. I. Hamad
 Packaging, labeling, and storage
• Unique aspect: product is packaged as part of the
manufacturing process. Most have a protective cap over
the mounting cup (made of plastic or metal) protects
against contamination and has a decorative function.
• Most unmedicinal aerosols have labels printed directly on
the container. Medicinal aerosols have a manufacture’s
plastic peel-away labels so the pharmacist can replace.
• Labels must warn users not to puncture, not store near
heat (over 49 C). Most are used in RT. Labeled with
regard to shaking before use, holding at the proper angle
and distance from target.

Dr. I. Hamad
 Proper administration of aerosols
• Written instruction with verbal assistance
• Some requires shaking, hold between the index finger and thumb.
• Coordination between inhalation
• Aerosol spacers: A spacer, used in conjunction with an MDI improves drug
delivery to the lungs and significantly reduces local and systemic side
effects from drugs, especially inhaled corticosteroids
• Young children with asthma are unable to use an MDI effectively without
the addition of a spacer. Small volume spacers such as the Babyhaler
(GlaxoWellcome) and Aerochamber (Trudell Medical, Canada) have been
developed for this purpose. These spacers consist of a facemask connected
to a cylindrical extension device via a one way valve. The facemask can be
replaced by a mouthpiece.
• Other Adv: aerosol velocity is reduced and droplet size is deceased because
there’s time for propellant evaporation (causing less deposition of
medication in the oropharynx)

Dr. I. Hamad
Pocket Chamber is a
compact aerosol spacer
device.
Fits virtually any metered
dose inhaler.
One-way silicone valve
avoids loss of medication by
poorly timed exhalation.
Whistle alert for excessive
inspiratory rate.

Dr. I. Hamad
• For topical administration of aerosols: patient should
clean affected area gently and pat it dry. Hold the canister
with the nozzle pointing toward the body area about 6-8
inches away, press down and cover the area. Allow spray
to dry, don’t cover unless instructed. Don’t direct it to
mouth or eyes. If intended for facial area, spray into the
palm and apply.

Dr. I. Hamad
 Topical aerosols
• Include antifungal agents: povidone iodine and tolnaftate
and thimerosal. Adrenocortical steroids betamethasone,
and local anesthetics
• Topical is convenient for patients; applied without using
of hands (less messy)
• Diadv: difficulty in applying it to small surface area and
cost.

Dr. I. Hamad
 Vaginal and rectal aerosols
• Foams containing estrogenic substances and
contraceptives are available (intravaginal). Package
contains inserter that’s filled with foam and contents are
placed in vagina. Foams are generally o/w emulsions (like
simple creams) water miscible and nongreasy.
• Rectal foams include ProctoFoam (Reed&Carnrick)
contains pramoxine hydrochloride to relieve
inflammatory anorectal disorders (See Fig. 14.18)

Dr. I. Hamad
Pharmaceutics I

I. Hamad, Ph.D.

1
 Why we need Dosage Forms?
Dosage form: physical forms of the pharmaceutical preparations with medications

A. A mechanism for dosing; precise, convenient, and safe delivery of the drug

B. Improve drug’s performance:

1. Protect active ingredients from external degrading
environment, e.g. light, oxygen, …
2. Protect active ingredients from physiologic degrading
environment, e.g. gastric acid
3. Provide optimal drug action through a proper route of
administration, e.g. ophthalmic antibiotics

2
 Why we need Dosage Forms?
C. Improve drug’s solubility, e.g. the use of
suspensions
D. Enhance drug’s release profile; controlled
and sustained release

E. Improve patient’s acceptance of the drug,

e.g. conceal bitter taste

3
 Routes of Drug Administration?
Choice of route of administration is influenced
by???
1. Desired site of action. E.g. skin infection??
2. Patient’s status. E.g. neonates and elderly??
3. Desired Kinetics of the drug; onset rate and duration.
E.g. liquid dosage forms vs. solid??
4. Amount/dose to be administered

5. Drug’s metabolism. E.g. first pass effect??

4
 Solutions
“liquid preparations that contain one or more chemical substances
(called solutes) dissolved in a suitable solvent or mixture of
mutually miscible solvents”. Because of their uses, they can be
classified into: oral, otic, ophthalmic or topical.
Classified into other dosage forms: syrups: aqueous sln containing
sugar. Elixirs: sweetened hydroalcoholic sln. Spirits: slns of
aromatic materials. Tinctures: sln prepared by extracting active
constituents from crude drugs

5
 Solubility
“The ability of a given substance, the solute, to dissolve in certain
solvent(s)”. Attractive forces between molecules lead to coherence
while repulsive prevent that.

Driving force for solubilization: breaking of solute-solute and solvent-

solvent interactions and formation of (stronger) solute-solvent forces
(the forces of attraction between the solute and the solvent molecules
must over come the substance’s intermolecular forces)

Attractive forces that hold molecules together: dipole-dipole, ionic,

hydrogen bonding, and London forces

6
Solubility

7
 Solutions
when a solution can be termed saturated?

Solubility, usually, indicates "saturation”

Saturation: maximum amount of a solute that can dissolve in a

certain quantity of solvent at specified conditions; pH,
temperature, pressure, …

Keep adding  stir  until precipitate

So the maximum possible concentration to which a pharmacist may prepare
a solution varies greatly and depends on the chemical constitution of the
solute ( you can also change other factors to improve solubility; different
solubilizing agents, different salts, pH)

8
• Temperature: important to determine solubility of a drug: most chemicals
absorb heat when they are dissolved and said to have a +ve heat of sln, so
solubility increases with an increase in temperature. Most reactions
between solvents and solutes are endothermic; absorb heat  positive
heat of solution  increase solubility with increased temperature
• Explanation: It is thought that at higher temperature water/solvent
molecules move faster which allow solute molecules to mix and keep in
contact with solvent molecules

• The average kinetic energy of the solute molecules also increases,

destabilizing the solid state. The increased vibration (kinetic energy) of
the molecules causes them to be less able to hold together, and thus
they dissolve more readily.

Pressure: generally, has no effect on liquid solutions but induces gas

solubility.
Solubility of a substance at a given T and P is constant; the rate of solution
depends on particle size (surface area) and extent of agitation.
 Solubility expression
Solubility is expressed in amount of solute (e.g. grams) per
volume of solvent (e.g. ml).

e.g. a solution of sucrose has solubility of 2 g/ml

If exact solubility has NOT been established, general

expressions of relative solubility are used (defined in the
USP)

10
 Descriptive Term Parts (ml) of solvent required for 1
part (g) of solute
Very soluble <1

Freely soluble 1-10

Soluble 10-30

Sparingly soluble 30-100

Slightly soluble 100-1000

Very slightly soluble 1000-10,000

Practically insoluble or insoluble > 10,000

11
 Solubility
pH: most drugs and excepients are weak bases or weak acids  react with
strong acids or bases to form H2O soluble salts

e.g. Weak base  soluble in acids  form H2O soluble salts  increase
pH  separate

In pharmaceutical industry, to enhance H2O solubility, organic compounds

are prepared in salt form (salts are formed by neutralization; acid + base)

e.g. while 5,000 ml water are required to dissolve 1 g morphine , only 16

ml are required to dissolve 1 g morphine sulfate (see Tab. 13.2)

12
 General rules of Solubility
 Like dissolves like: solvent has similar chemical structure to solute..
Organic compounds in organic solvents (organic compounds might be
somewhat water soluble if they are highly polar and can form hydrogen
bonds with water)

 Free drugs/organic compounds dissolve more in organic solvents

 more polar groups  ↑ H2O solubility; more H-bonds

 Higher molecular weight  ↓ H2O solubility, e.g addition of halogen

atoms into a molecule.

See Tab. 13.3

13
 General rules of solubility
 Liquids with similar structures (similar type of
intermolecular forces) will be soluble in each other in all
proportions

 Alcohol Solubility decreases as length of carbon chain

increases because as the chain gets longer, more H-bonds in
the water must be broken to make room for the alcohol.

Not enough H-bonds can be reformed to compensate

14
 General rules for solubility of
organic compounds
 Molecules with 1 polar functional group are usually
soluble to total chain lengths of 5 carbons

 Branched molecules are more soluble than the

corresponding straight-chain compounds

 H2O solubility decreases with increase molecular weight

 Increased structural similarity between solute and

solvent increases solubility

15
 General rules for solubility of
inorganic compounds
 Monovalent anions and cations of ionic compounds are
generally H2O soluble. E.g. NaCl

 If only one of the two ions is monovalent, compound is

expected to be H2O soluble, e.g. Na2SO4

 If both ions are multivalent, compound is expected to have

poor H2O solubility, e.g. CaSO4

16
 General rules for solubility of
inorganic compounds
 Ammonium and quaternary ammonium salts are generally
H2O soluble

 Chlorides, bromides, and iodides are generally H2O soluble

 Salts of alkali metals are expected to be H2O water soluble,

e.g. Na+

 Sulfates and sulfites and thiosulfites are generally water

soluble

 Phosphates, carbonates, silicates, are generally water

insoluble. 17
 Rate of solution
The rate (measure of how fast) the substance dissolves in
certain quantity of the solvent.

Factors affect rate of solution:

1. Size of particles:

When a solute dissolves, solvent-solute interaction occurs

only at the solute’s surface.

Decreasing size by breaking solute into smaller pieces

increases the surface area and enhances the solubility
18
 Factors affect rate of solution
Size of particles:

In pharmaceutical preparations particle size of active and

inactive ingredients is reduced by
 grinding using mortar and pestle (in laboratory and small scale
preparations)

 and the use of micronizers in pharmaceutical industries (large

scales)

19
 Factors affect rate of solution
2. Stirring
Mechanism: brings fresh portions of the solvent
in contact with the solute
3. What is the amount of the solute already in
solution????
4. Temperature?

20
 Considerations for solvent selection in
pharmaceutical dosage forms

1. Solubility (Main)
2. Toxicity
3. Palatability, odor, and color
4. Viscosity
5. Inertness
6. Cost
7. Clarity
8. Compatibility with other formulation ingredients

Generally for oral, ophthalmic, and injectable formulations, H2O

is the preferred solvent
21
 Solvents for liquid pharmaceutical
preparations
Purified water

 Naturally occurring water, including tap water, is NOT

acceptable for the manufacture of most pharmaceutical
products
 Because of dissolved and undissolved organic compounds,
microorganisms, and dissolved inorganic salts (e.g. Na, Ca,..)
and gases (e.g. CO2)  incompatibilities with the medicinal
agent and the dissolved solids

22
 Solvents for liquid preparations

Purified water

 Signs of incompatibility: precipitation, discoloration,

effervescence, …

 Purified water is prepared by: distillation, ion exchange,

or reverse osmosis

23
 Solvents for liquid preparations
Alcohol
Ethyl alcohol, ethanol, CH3CH2OH

 Second to H2O as most commonly used solvent

 Miscible in water in all proportions (with water forms hydroalcohol which

dissolves both water and alcohol soluble substances)

 Dissolves many water insoluble ingredients; drugs, flavorants, antimicrobials..etc

 Preservative in liquid products

 Primary solvent for many organic compounds

 Toxic concerns: FDA recommended alcohol content for OTC children below 6
years is limited to 0.5%. 6-12: 5%. Over 12 not more than 10%

24
 Alcohol

 Limitations: toxicity especially in children

 Purity: 94.9-96.0% v/v
 Dehydrated alcohol: ≥ 99.5%, considered water-free alcohol

 Hydroalcoholic mixtures: combination of H2O and ethanol

that dissolve both alcohol and H2O soluble drugs. May vary
the alcohol ratio to improve solubility

25
 Solvents for liquid preparations
Glycerol
Glycerin, CH2OH-CHOH-CH2OH

 Viscous liquid

 Sweet taste

 An alcohol

 Miscible with water and alcohol/ethanol

 Preservative

 Because of high viscosity, solubility is slow  dilution with

alcohol
26
 Solvents for liquid preparations
Propylene glycol
 CH3CH(OH)-CH2OH, an alcohol

 Viscous liquid

 Miscible with water and alcohol/ethanol

 Sweet

 Preservative effect

 Used in combination with other solvents in oral

preparations
27
 Rubbing Alcohol

 Is 70% ethanol by volume + denaturants (substance that

render alcohol unfit to drink; gives noxious flavor and
odor; de. benzoate) + stabilizers+ bitter substance

 Used, externally, as a germicide and a skin cleanser prior

to injection

28
 Isopropyl rubbing alcohol
 Isopropyl alcohol 70% by volume + water with or without
color additives and perfume oils

 Used externally as disinfectant (usually applied by diabetic

patients in preparing needles) and vehicle for topical drug.

29
 Preparation of Pharmaceutical Solutions
 Most pharmaceutical products are unsaturated with solutes

 Strength of pharmaceutical products is expressed as percentage and

rarely (for diluted products) as ratio:

 Percent weight in volume % w/v 1g/100ml

 Percent volume in volume % v/v 1ml/100ml

 Percent weight in weight % w/w 1g/100g

 Ratio weight in volume -:-- w/v 1:1000w/v: 1g/1000ml

 Ratio volume in volume -:-- v/v

 Ratio weight in weight -:-- w/w

30
 Preparation of Pharmaceutical Solutions
 Examples:

 Hydrocortisone ointment 1% w/v means 1 gram of the drug in each

100 ml of the vehicle

 Water solubility of a drug = 2% means you can dissolve 2 grams in

100 ml water

 Advantage of rapid solution by heat (or in case of volatile solute or

solvent) may deteriorate some drugs, so avoid..

 Most slns are prepared by simple mixing. On large scale, industries

use large mixing vessels.

31
 Oral Solutions
 Major components:
 Active ingredients; drugs, medicinal agents

 Excipients, examples:

 Solubilizers, enhance solubility

 Flavorants; flavoring agent: enhance palatability

 Colorants; coloring agent: attractive appearance

 Sweeteners, enhance palatability

 Preservatives: prevent microorganism growth

 Stabilizers: maintain physical and chemical stability, e.g.

antioxidants, chelating agents, and buffers to prevent
decomposition 32
 Solubilizers
 A substance used to help solubilize another; which increases
the solubility of a relatively insoluble compound to allow it to
dissolve in water.

 Type of surfactants.

33
 Antioxidants
 Inactive ingredients added to pharmaceutical preparations to
prevent deterioration of the preparation by oxidation

 Such compounds get easily oxidized and preserve the other

ingredients from oxidation

 Examples, sodium bisulfite

34
 Dry Mixtures for Oral Solutions,
Reconstitutables
 Dry mixtures (for preparation into solution or suspension prior to use
(reconstitution). For some medicinal agents (antibiotics) which have low
stability in aqueous soln, i.e., shelf life.

 Have all components (drug, flavorant, preservative, colorant,…) in dry

forms

 Powder is reconstituted by the addition of a specified amount of purified

water and shaken very well

 The reconstituted solution is stable for 7-14 days, depending on the

manufacturer’s instructions. Discard if left over.

35
 Dry Mixtures for Oral Solutions,
Reconstitutables
 pharmacist should assist the patient with dosage, directions
for use and storage.

 Avoid chemical instability; when the drug is not stable

long enough in an aqueous medium

Example: while penicillin suspension’s shelf life ~ 14

days, dry penicillin has at least 2 years of shelf life

 Other advantages: reduces the weight of the final product 

easier and cheaper shipping

36
 Syrups
Viscous concentrated aqueous preparations of sugar intended
for oral use.
Syrups are specially useful for:
 Children and elderly who can not swallow solid dosage forms
 Masking the bitter taste of certain medications
 Water soluble drugs (has little or no alcohlol, so favored by
parents)
 Most antihistamines and antitussive drugs
 Medicated syrups are employed for the value of the active
agent (prepared from the starting materials; all individual
components of syrup plus the active)

37
 Syrups
Non-medicated syrups/flavored syrups:
sugar or sugar substituent
flavoring agent
Medicated syrups:
sugar or sugar substituent
active ingredient
± flavorants

38
 Syrups
Examples of non-medicated syrups
 Cherry syrup: sucrose, 47% v/v cherry juice, acidic pH 
useful for drugs stable in acidic pH
 Ora-Sweet: sugar free, acidic pH
 Syrup; also known as simple syrup: 85% sucrose in purified
water
The pharmacist may be asked to prepare oral solutions (e.g.
syrups) from tablets or capsules
See tab. 13.7 for some e.g.

39
 Components of Syrups
A. Active ingredient(s)
B. Excipients:
1. Sugar or sugar substituent
2. Preservative
3. Flavorants
4. Colorants
5. Others: stabilizers, thickeners, …
Excipients: inactive pharmaceutical ingredients
Viscosity, sweetness/sugar, and flavors help mask taste.
In case of sugar-free syrups: a substance that creates viscosity is
added

40
 Syrups

Syrups usually have low solvent capacity for water soluble drugs
because of the strong interaction between sucrose and water
molecules  difficult for the solute to form bonds with water

For this reason the drug is usually dissolved in water before the
introduction of sucrose or syrup

41
 Components of Syrups, sugar
Preparation of Syrup, NF: simple syrup (85% sucrose)
specific gravity = 1.313 g/ml  weight of 100 ml = 131.3 g
 85 g sugar + (131.3 – 85 = 46.3) g water
Solubility of sugar is 2 g per 1 ml water  to dissolve 85 g we
need 42.5 ml water  water available = 46.3 – 42.5 = only
3.8 ml per 100 ml syrup
However, this small excess of water (3.8 ml) is very important to
maintain physical stability. At saturation, some sucrose may
crystallize at cooler temperature  work as a nuclei that
initiate chain reaction  separation of sucrose even at
concentrations below its solubility  this may encourage
microbial growth
42
 Components of Syrups
Viscosity masks taste by creating a physical concealment of
the active drug  only small portion of the dissolved drug
makes contact with the taste buds in the tounge, the remaining
passes them and down the throat
Additional benefit in antitussive syrups:
Viscose syrup soothes the irritated throat as it passes over it.

43
 Components of Syrups, preservation
Preservation of syrups
1. Adding preservatives, e.g. benzoic acid, sodium benzoate,
alcohol, glycerin,…
2. High concentration of sucrose
3. Storage at low temperature and tight containers
Preservatives:
Amount varies depending on:
1. Proportion of water available for microbial growth
2. Preservative nature of other formulative ingredients, e.g.
alcohols
3. Capability of the preservative itself

44
 Components of Syrups, preservation
Preservatives:
1. Benzoic acid: 0.1 – 0.2%
2. Sodium benzoate: 0.1 – 0.2%
3. A paraben or a combination of methyl parabens, propyl
parabens, and butyl parabens: total ~ 0.1%
4. Alcohol*: not considered as a primary preservative

45
 Components of Syrups, Flavorants
Flavorants:
Used to enhance patients acceptance
Most flavorants have acceptable water solubility; however,
solvents (e.g. Alcohol) may be added to improve solubility
 Natural flavoring agents

 Synthetic

Examples of natural agets, volatile oils (orange oil), vanillin.

46
 Components of Syrups, Colorants
Used to impart color to liquid and solid preparations
(mint>green, choc>brown)
 Most coloring agents currently used in pharmaceutical
preparations are synthetics and water soluble.
 Inert
 Stable at different pH and light

47
 Components of Syrups
Sucrose- and non-sucrose-based syrups
 Sucrose is the most commonly used sugar in syrups; both
medicated and non-medicated.
 Sucrose may be replaced, in part or in whole, by other sugars
like sorbitol (reduced glucose, used in sugar-free
preparations) or sweet compounds like glycerol or propylene
glycol
 E.g. Sorbitol Solution, USP; 64%

48
 Components of Syrups
 Sucrose may be replaced by non-glycogenic compounds such as
methylcellulose and hydroxy ethylcellulose  non-biodegradable:
no hydrolysis or absorption
 Give viscosity similar to sucrose
 However, artificial sweeteners should be added
 For diabetic patients: non-glycogenic compounds + sweeteners are
used
 Other polyols, such as glycerol or sorbitol, may be combined with
sucrose to:
 Retard sucrose crystallization
 Contribute to the sweetness
 Increase solubility of the ingredients

49
 Syrups
• Contain 60-80% sucrose: sweetness, viscosity
and also coz of its inherent stability (compared
to diluted: yeasts and molds)
 Syrups, other uses
 Syrups are also used to apply coatings to tablets
especially those with disagreeable aroma or acrid taste
 Non-medicated syrups are used to prepare liquid dosage
form from solid ones (e.g. tablets and capsules)
 If all components are water-soluble such as in some
capsules solution should result
 If some ingredients are water-insoluble like in tablets
suspension would result

51
 Storage and labeling
 Syrups are usually made to be consumed within a few months
 Bottles should be filled completely if possible
 Tightly closed containers
 Cool and dark place

52
 Antihistamine Chlorpheniramine Syrup, USP
Chlorpheniramine maleate 0.4 g
Glycerine 25.0 ml
Syrup 83.0 ml
Sorbitol solution 282.0 ml
Sodium benzoate 1.0 g
Alcohol 60.0 ml
Colour and flavor q.s.
Purified water, to make 1000.0 ml

53
 Methods of Syrup Preparation
Depending on the physical-chemical properties of ingredients
• Solution With the Aid of Heat
• Solution by Agitation Without the Aid of Heat
• Addition of Sucrose to Medicated Liquid or to Flavored
Liquid
• Percolation

54
 Solution With the Aid of Heat
Procedure:
1. Purified water is heated up to 85 ⁰C sucrose is added and
agitated vigorously until sugar is dissolved
2. Add other heat-stable components to the hot syrup
3. Cool mixture
4. Adjust volume by the addition of purified water
5. If Heat-labile components required; now added after cooling.
E.g. alcohol and volatile oils
6. Adjust to the specified volume

55
 Solution With the Aid of Heat
Advantages:
1. Quick preparation of syrups (sugar dissolving)
2. Heat enhances the “rate of solution”

Disadvantages:
1. Unsuitable for heat-sensitive compounds
2. Excess heat may cause hydrolysis of sucrose into glucose and
fructose (invert sugars)
 Acidity (hydrogen ions) enhances above reaction
3. Invert sugars are sweeter than sucrose (sweetness changes),
colour change (caramelizes), enhances microbial growth

56
 Solution by Agitation Without the Aid of
Heat
Avoid sucrose inversion
Procedure:
1. Place sucrose and water in large size vessels then mix to form
syrup
 At an industrial scale, large tanks equipped with mechanical mixers or
agitators are used
2. Other ingredients are dissolved in the minimal volume of
water and then mixed with syrup (viscous, amount of
available water)
Viscosity and volume of available free water
Adv? Disadv?

57
 Addition of Sucrose to Medicated Liquid
or to Flavored Liquid
Simple mixing of medicated liquids (tinctures or fluidextracts)
with syrups.
tinctures or fluidextracts contain alcohol soluble ingredients

Alcohol is often an ingredient in syrups prepared using this

method because tinctures or fluidextracts are prepared in
alcohol or hydroalcohol solvents.
Syrup in this way usually develop precipitates (when alcohol is
mixed with water). So: mix tincture with water, allow it to
stand and separate, filter, and dissolve sucrose in the filtrate
(not when precipitates are active ingredients)

58
 Percolation
Percolation: A process to extract the soluble constituents of a plant with
the assistance of gravity.
Extraction of a compound by the slow passage of the solvent through a
column of the compound. (then addition of sucrose to form a syrup)
Or: Either purified water or the source of active agent is passed slowly
through a bed of crystalline sucrose, thus dissolving it and forming
a syrup.

59
 Elixirs
Clear, sweetened, usually flavored, hydroalcoholic solutions
intended for oral use.
Dose is usually adjusted to 5-10 ml.
 Non-medicated elixirs:
No therapeutic agents
Used as vehicles for other elixirs (should pay attention to the
alcohol amount) or in preparing tablets in the pharmacy into
liquid dosage form
e.g. aromatic elixir
 Medicated elixirs:
Have therapeutic agent(s).

60
 Elixirs
 Sometimes elixirs are preferred to syrups
because:
 Solubilization of water- as well as alcohol-soluble
drugs
 Ease of preparation (simple solution)
 Better stability (maintain water & alcohol
solubility)
 Compared to syrups, elixirs are less sweet and
less viscous  less masking of taste

61
 Elixirs
 Proportion of alcohol depends on water solubility of the
ingredients
 for highly water-soluble compounds less alcohol is
required
 Alcohol content: 5-40%
 Other solvents (e.g. glycerin, syrup, propylene glycol) may be
used as adjunctive solvents to improve solubility. Which
enhances stability

62
 Elixirs
 Elixirs composition:
A. Active ingredient
B. Excipients
 Water
 Alcohol
 Flavorings: all elixirs contain flavorants to improve taste
 Colorants: most elixirs
 Preservatives. Elixirs that contain > 10-12% alcohol are self-preserving
 usually do not require preservatives
 Sweetener:
 Sucrose, sucrose syrup or sorbitol
 High alcoholic concentration  artificial sweetener (e.g.
saccharine) are preferred because sucrose is less soluble in alcohol

63
 Elixirs
 Usual dose for adults 5-10 ml
 The major disadvantage of elixirs is alcoholic content
especially in those who have to avoid alcohol like children
 Storage:
Tight, light resistant containers
Protect from excessive heat

64
 Preparation of Elixirs
 Simple solution with agitation and/or by admixture of 2 or
more liquid ingredients:
1. Dissolve alcohol-soluble ingredients in ethanol
2. Dissolve water-soluble ingredients in purified water
3. Aqueous solution is gradually added to alcoholic rather than the
reverse (enough alcohol>> no seprn.!!)
4. Volume is adjusted with the specified vehicle

65
 Preparation of Elixirs
 If the mixture becomes cloudy, this means that the flavoring
oil has separated because of the reduced alcoholic
concentration in the final mixture
 If this occurs, permit elixir to stand for several hours until all oil
globules coalesce and then filter to remove
 You can use talc…
 Presence of glycerin, syrup…etc assists in dissolution of solute but
increases viscosity>> slow filtration.

66
 Tinctures
 Alcoholic or hydroalcoholic solutions prepared
mainly from vegetable materials (plant extracts) or
rarely from chemical substances. (different strengths
and alcohol content)
 Can be oral or topical tinctures Contain alcohol 15-
80%
 Other solvents (e.g. glycerin) may be included to
improve solubility

67
 Tinctures
 When prepared from chemical substances tinctures
are prepared by simple solution
 When prepared from plants, ethanol ± water is used
to extract the medicinal agent from plants
 Tinctures cannot be successfully mixed with too
diverse solvents because of ingredient’s limited
solubility. The drug usually has poor water solubility

68
 Tinctures
 Advantages of alcohol:
 Solubilizes active ingredient
 Protects against microbial growth

 Disadvantages of alcohol:
 High alcohol intake especially for children and elderly;
other liquid forms are preferred

69
 Tinctures
 Storage:
 Very tight stopper
 Avoid excessive temperature
 Light-resistant containers and protected from direct
sunlight; because most extractives are photo-sensitive

70
Cardamom Tincture, BP
Cardamom oil 3 ml
Caraway oil 10 ml
Cinnamon oil 10 ml
Clove oil 10 ml
Strong ginger tincture 60 ml
Ethanol (90%), to make 1000 ml

Uses: carminative, added as a pleasant aromatic to several mixtures, tinctures.

71
 Topical Solutions
 Vehicle:
1. Aqueous or
2. Alcohol; e.g. tinctures for topical use
3. Rarely, oleaginous
 Usually packaged with an applicator attached to the cap or in
plastic squeeze bottles
 Prepared by:
 Simple solution; mixing and dissolving
 Chemical reaction

72
 Topical Solutions
 Many topical solutions are self-preserved because of solvent
or co-solvent action. If not, a preservative is added
 Many topical solutions contain a dye to delineate the area of
application to the skin

73
 Topical Solutions
1. Sprays
Aqueous or oleaginous solutions in the form of coarse droplets or
as finely divided solid to be applied topically, to the skin or
most usually to the nasopharyngeal tract.
 E.g. intranasal decongestants, anti-inflammatory, or
antibiotics
 Promising route of administration
 To break up a solution into small particles (spray): plastic
spray bottles used.

74
 Topical Solutions, Sprays
A. Advantages of intranasal sprays:
 Noninvasive
 Quick
 Systemic delivery
 Bypass GIT
B. Throat sprays:
 Contain antiseptics, deodorants, and flavorants
 May be used to treat halitosis, sore throat, laryngitis

C. Skin sprays:
 Contain local anesthetics, antiseptics, skin protectants, and
antipruritics
 Used to treat sunburns and heat burn conditions
76
 Topical Solutions
2. Hydrogen Peroxide Topical Solution
 2.5-3.5 % (w/v) H2O2.
 Local anti-infective for topical use on skin and mucous
membranes
 Mechanism of action: strong oxidizing agent which lasts only
for short period
 A preservative (≤ 0.05%) may be added
 Prepared by chemical reactions, e.g. reacting barium peroxide
with phosphoric acid:
BaO2 + H2SO4  BaSO4 + H2O2
 Clear, colorless liquid, odorless

77
 Topical Solutions
 Decomposes to form water and oxygen
 Decomposition is enhanced by:
 light
 Heat
 Stored in tight, light-resistant container, and avoid excessive
temperature

78
 Topical Solutions
3. Povidone Iodine Topical Solution
A an aqueous solution contains iodine and polyvinylpyrrolidone (a
polymer).
 10% iodine w/v
 Iodine and ployvinylalcohol forms a complex.
 Iodine is slowly released from the complex when applied to
the skin
 Uses: local anti-infective solution
 Commercial name: Betadine®

79
 Topical Solutions
4. Topical tinctures
Iodine Tinctures
 Prepared by dissolving 2% iodine crystals and 2.4% sodium
iodide in sufficient amount of alcohol then volume is adjusted
with water.
I2 + NaI ↔ NaI3

 This reaction prevents the formation of “ethyl iodide” from

interaction of ethanol with iodine which would result in loss
of the antibacterial activity
 Alcohol 40-50%
 Uses: local anti-infective solution
80
 Nonaqueous Solutions
I. Liniments
Alcoholic or oleaginous solutions or emulsions of various
medicinal agents intended to be rubbed on the skin.
 Liniments should not be applied to a broken skin

1. Alcoholic or hydroalcoholic liniments are useful when rapid

penetration of the skin is desired such as in counterirritants

2. Oleaginous liniments are beneficial when message is desired.

They are usually less irritating to the skin than the alcoholic
ones. Fixed oils such as almond oil or volatile such as
wintergreen oil may be used as a solvent.
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 Nonaqueous Solutions
Liniments
Labeling
 External use only and never be taken internally
 For emulsion liniments: shake well before use
 Store in a tight container

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 Nonaqueous Solutions
II. Collodions
Solution preparations of pyroxylin dissolved in a mixture of
ethanol and ether with or without a medicinal agent
 Pyroxylin = nitrocellulose; prepared by adding nitric acid to
cotton
 When dried it looks like cotton but it is harsh to touch
 Highly flammable
 Highly volatile
 When applied to the skin using a brush, solvents dry up
quickly and leave a very occlusive and protective coating
made of a film of pyroxylin ± the drug

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 Nonaqueous Solutions
Collodions
 Labeling and storage:
Store away from flames; inflammable
Tight container
Protect from light
External use only
Must be applied to dry tissue to adhere

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 Nonaqueous Solutions
Collodions
Example:
 Collodion
Just the vehicles and pyroxylin; no medication
Used to hold edges of an incised wound together

 Salicylic Acid Collodion

10% salicylic acid
Keratolytic to remove warts/corns form the toes
Collodions could be made more flexible by the addition 2% camphor
and 3% castor oil

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 Vaginal and Rectal Solutions
Solutions intended to be applied into the vagina or the
rectum

 They are prepared as liquid solutions, solution

concentrate (to be diluted with warm water before
use), or powder to be dissolved in water before use

 Vaginal douche used for irrigation and

cleansing; it usually contains antimicrobial,
detergent (SLS), astringent, and aroma

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 Vaginal and Rectal Solutions
 Rectal solutions:
 Retention Enemas: to administer a drug rectally for
systemic absorption.
it may be useful to avoid GIT side effects or instability, or
to treat a local disease in the rectum or the colon
example, locally, hydrocortisone
systemically, aminophylline

 Evacuation Enemas: to cleanse the bowel.

Usually contains a stool softener, e.g. docusate
Packaged in squeeze disposable plastic bottles
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