ISSN: 2277- 7695

CODEN Code: PIHNBQ

ZDB-Number: 2663038-2
Received: 11-03-2013 IC Journal No: 7725
Accepted: 12-05-2013
Vol. 2 No. 4 2013
Online Available at www.thepharmajournal.com

THE PHARMA INNOVATION - JOURNAL

Formulation and Evaluation of Ciprofloxacin

Microspheres for Nasal Drug Delivery
S. Duraivel*1, Harish.G 1, B. Pragati Kumar1, Debjit Bhowmik1, Sunil Midimalapu2

1. Nimra College of Pharmacy, Ibrahimpatnam, Vijayawada, Andhra Pradesh, India.

[[email protected]]
2. Jayamukhi College of Pharmacy, Narsampet,Warangal, Andhra Pradesh, India.

The aim of the study was to evaluate ciprofloxacin-hydrochloride loaded microspheres using copolymers
synthesized from acrylic and methacrylic acid esters as a the retardant material for nasal administration..
Microspheres prepared by emulsion solvent diffusion method using an acetone and dichloro methane system.
Formulation parameters and processing parameters like ratio of drug to polymer (1:1, 1:1.5, 1:2 and 1:3)
concentration of aerosol, volume of water and stirring speed were optimized. Aerosil was used as the inert
dispersing carrier to increase the dissolution rate. The prepared microspheres characterized for their micromeritic
propertics and drug loading, as well as Differential scanning calorimetry and scanning electron microscopy. The In
vitro release studies performed in Phosphate buffer PH 7.4. The prepared microspheres should white, free flowing
and spherical in shape. The drug-loaded microspheres showed 86-96% of entrapment and release contected up to 8-
10 hr.
Keyword: Ciprofloxacin Hydrochloride, In vitro Release Studies, Emulsion Solvent Diffusion Method,
Microspheres for Nasal Administration.

1. Introduction in the gastrointestinal tract being prone to first-

Intranasal delivery is suitable for the local and pass effect and must
systemic delivery of diverse therapeutic be administered by injection The objective of the
compounds. Among the non-invasive routes, present study is to prepare the sustained release
nasal administration offers promising potential as microspheres of ciprofloxacin by improving the
a viable alternative for the delivery of some entrapment efficiency and patient compliance and
drugs.8 Hence, a surge of interest led to many thereby decreasing the toxicity, dosing frequency,
investigations involving the nasal cavity as a cost of the drug, avoiding the first pass
feasible site for the administration of much metabolism, and maintain the optimum
therapeutic agents. The nasal route is therapeutic drug level for prolonged period.
conventionally used for drug delivery for Ciprofloxacin is a broad-spectrum antibiotic
treatment of local diseases . In the recent years, active against gram positive and gram negative
this route has received special attention as a bacteria[6]. All type of microspheres that has been
convenient and reliable method for the systemic used as an nasal drug delivery are water soluble
delivery of drugs, especially those that are but absorbed water into sphere matrix, resulting
ineffective by oral route due to their metabolism in swelling of spheres[12]. The eudragit

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The Pharma Innovation - Journal

microspheres system was effective as an crystallization technique has been accepted as a

absorption enhancer for ciprofloxacin. The quassi useful technique for a particle design for
emulsion solvent diffusion of ciprofloxacin pharmaceuticals.
microspheres is simple, suitable, and reproducible Weighed amount of ciprofloxacin was dissolved
method to obtained ciprofloxacin microspheres. with Eudragit S 100 in a mixed solution of
acetone and Di choloro methane. Then aerosol
2. Materials and Methods was suspended uniformly in the drug polymer
Ciprofloxacin is procured by Vital therapeutics, solution under vigorous agitation. The resultant
secundrabad, Eudragit S100 gift sample from drug-polymer suspension was poured into 150 ml
Evonik Roehm Pharma polymers, Mumbai, distilled water containing (0.02-0.15%) of sodium
Aerosil purchased from Yerrow chem., Products, deodile sulphate (poor solvent). Under agitation
Mumbai, Acetone, Dicholo methane purchased (400-700) and thermally controlled at 38 c.
from Merck Pvt. Ltd Mumbai. After agitation the system mixed for 20 min., 15
ml of poor solvent was added slowly, and
2.1 Standard Graph of Ciprofloxacin In agitation was continued for another 40 min until
Phosphate Buffer PH 7.4 the translucent quasi-emulsion droplets turned
100 mg of ciprofloxacin was taken in 100 ml of into opaque microspheres. The solidified
phosphate buffer (PH 7.4). Aliquots of 10 ml microspheres were recovered by filtration and
from stock solution was taken and diluted to 100 washed with water. The resultant microspheres
ml with phosphate buffer to get 2, 4, 6, 8 and 10 were dried in an oven at 5 0 C for 6 hrs.
mcg/ml. The absorbance of the solution was Formulation containing drug polymer ratio (eu
measured at 271 nm on a spectrophotometer. RSPO) 1:1, 1:2, 1:3 were coded as F1, F2, F3.
While formulation containing drug (Eu.S100) .
2.2 Peparation of Ciprofloxacin 1:1, 1:1.5, 1:2, 1:3 were coded as B1, B2, B3, B4
[1,3.4,5]
Microspheres microsphere dried at room temperature were then
2.2.1 Quasi Emulsion Solvent Diffusion weighed and the yield of microspheres prepation
Method was calculated using following formula
Microsphere was prepared by quasi-emulsion
solvent diffusion method. The spherical

Table 1: standard ciprofloxacin in phosphate buffer PH 7.4

S.No. Concentrati Absorbanc Absorbance Absorbance Avg absorbance

on(mcg/ml) e (mcg/ml) (mcg/ml) (mcg/ml) (mcg/ml)
1. 2 0.149 0.138 0.162 0.148
4 0.321 0.316 0.329 0.322
2.
3. 6 0.474 0.487 0.470 0.477
4. 8 0.619 0.611 0.631 0.620
5. 10 0.751 0.749 0.755 0.751

2.2.2 Drug Interation Study[2,3] Drug loaded microspheres’ (100 mg) were
Drug and polymer interaction studies are carried suspended in buffer solution followed by
out by UV-spectroscopy, Scanning electron sonication for about 20 mins. It was shaken for
microscopy and different scanning calorimetric. another 20 mins in a rotary shaker for the
complete extraction of drug from the
3. Result and Discussion microspheres. The resultant solution was filtered
3.1 Encapsulation Effiency 12,13 through 0.45 mcg membrane filter. Drug content

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The Pharma Innovation - Journal

was determined by UV visible spectrophotometer efficiency of 87.7% with increasing the Eudragit
at 271 nm. S100 ratio to B2(1:1.5) B3 (1:2) and B4 with
Encapsulation efficiency was carried out with two encapsulation efficiency of 90.2, 93.5 and 95.1
polymers, Eu.S100 and Eu RSPO. Encapsulation was observed.
efficiency found to be increase with polymer Encapsulation efficiency was increased with
concentration in the formulations, it was observed increase in polymer concentration in the
with both polymers. In the formulation prepared formulation. Encapsulation efficiency of 63-85%
with Eudragit RSPO, the percentage of was observed in the microspheres prepared with
encapsulation efficiency ranged from 83-85%. In Eudragit RSPO(F1,F2,F3) .And that of 86-96%
formulation F1 with drug polymer ratio of 1:1 was observed in the microspheres prepared with
resulted as 84.8% of encapsulation efficiency Eudragit s100(B1,B2,B3,B4). It is so because the
similarly with formulation F2 and F3 containing higher the polymer to drug ratio, the higher
drug polymer ratio 1:1 and 1:3 found to be 83% probability of the drug surrounded by polymer,
and 85% respectively which acts as a barrier to prevent from diffusion
Eudragit formulations B1 and B4 drug loading of drug into the external medium. However, the
capacity found to be 90.2 to 95.1%. In the ratio of encapsulation efficiency depends on the polymer
drug to polymer resulted in encapsulations proportions.

%
encapsulation
effiency

Formulation code

Fig 1: Effect of drug to polymer ratio in entrapment efficiency

Table 1: Effect of drug to polymer ratio in entrapment efficiency

Formulation code % encapsulation efficiency

F1 84.8
F2 83
F3 85
B1 87.7
B2 90,2
B3 93.5
B4 95.1

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The Pharma Innovation - Journal

3.2 Particle Size Determination[7,9,12,14,15] concentration leads to an increase of the emulsion

The formulated microspheres were evaluated for drop let size.. However, the particle size was
the paricle size with the optical microscope. The observed in the microspheres prepared with
increase in the viscosity with increase in polymer Eudragit S100.

Table 3: Effect of drug to polymer ratio on mean particle size

Range of Particle
S.No. Formulation code Mean SD( mcg)
Size(mcg)
1 F1 13.6-21.5 17.55
2 F2 12.2-20.7 16.45
3 F3 15.5-23.1 19.3
4 B1 12.3-19.8 16.05
5 B2 14.1-20.5 17.3
6 B3 18.2-20.1 19.15
7 B4 10.5-18.5 14.05

Particle size

Formulation code

Fig 2: Effect of drug to polymer ratio on mean particle size

3.3 In vitro Drug Release Study[11,16,18,19] release 80%, 82.5%, 88.2%, and 98%. These In
The release rate ciprofloxacin from the vitro release studies indicated that ciprofloxacin
microspheres could be modulated with adjusting had been highly dispersed at the ratio, so as an
the ratio of Eudragit S100 to aerosol in the amorphous state. As dispersing carriers, aerosol
formulation. There is relatively minor increase in could improve apparent solubility and dissolution
the drug release rate when the ratio of the amount rate of ciprofloxacin efficiently.
aerosol to ciprofloxacin was increased from 1:1.5
to 1:2. The In vitro drug release profile with
formulations B1, B2, B3 and B4 are found to

Table 4: In vitro drug release data for ciprofloxacin formulations

Time(min) B1 B2 B3 B4
0 0 0 0 0
30 61.2 61.2 66.2 79.5
60 67.2 67.2 69.5 85.6

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The Pharma Innovation - Journal

120 71.5 72.6 74.3 90.4

240 75.4 77.8 80.2 98.09
360 80.2 82.5 88.2 95.35
480 78.2 78.2 78.2 95.7
600 70.1 71.1 69.3 92.5

B1
B2
% drug release
B3
B4

Time(min)

Fig 3: In vitro drug release data for ciprofloxacin formulations

3.4 Drug Release Models[15,16,17,18] models. The formulation B4 followed Higuchi

Data obtained from In vitro release studies were square root of time dependent model provided an
evaluated kinetically table present the co-relation ideal drug release rate, which is confirmed by
co efficient of formulations calculated according comparing all formulation co relation co efficient
to zero order first order, and Higuchi kinetic for Higuchi model.

Table 5: In vitro release kinetic parameters of ciprofloxacin microsphere

Types of model B1 B2 B3 B4
Zero order 0.6882 0.5627 0.6921 0.6806
First order 0.7632 0.6251 0.7362 0.8838
Higuchi model 0.8345 0.7924 0.912 0.9216
4. Conclusion
3.5 Ex-Vivo Permeation Studies[17,18] The present study investigates the feasibility of
Ex-vivo permeation study carried out by taking nasal delivery of ciprofloxacin microspheres
25 ml of diffusion media in a receptor formulated with various methods with acrylic
compartment and 100 mg of microspheres acid co polymers and evaluates the mechanistic
suspension in donor compartment, samples aspects of nasal route. The result based on In
collected at different time points and subjected vitro drug release studies microspheres prepared
for analysis. The amount of ciprofloxacin with 3% Eudragit S100 found to be an optimized
permeated at different time points was calculated formulation. The optimized formulation released
using the strait line equation of standard graph. 98% of the ciprofloxacin with in 6 hrs, and found
to follow Higuchi model of drug release. In near
future this route of administration will become

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The Pharma Innovation - Journal

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