The objective of this study was to develope an ophthalmic insitu gel of diclofenac potassium and to carry out evaluation tests to identify the most ideal formulation. Insitu gels for ocular drug delivery - Liquid upon instillation ( solution/suspension) -Visco-elastic gel in cul-de-sac - Increased precorneal residence time Diclofenac potassium -Non Steroidal Anti-inflammatory Drug (NSAID) -Treatment of miosis, post operative inflammation in cataract surgery.

1. Fabrication of Ophthalmic Insitu gel of
Diclofenac potassium and its evaluation
Subimol S , Ani Sree G S , Radhakrishnan. M
• Department of Pharmaceutics, Erode College of Pharmacy, Erode, Tamil Nadu, India
• Department of Pharmaceutics, Jamia Salafiya Pharmacy College, Pulikkal, Malappuram,
Kerala, India
• Department of Pharmaceutics,Kamalakshi Pandurangam College of Pharmacy,
Tiruvannamalai, Tamil Nadu,India.
Scholars Academic Journal of Pharmacy (SAJP); 2013; 2(2):101-106
Published in:

2. INTRODUCTION
 Insitu gels for ocular drug delivery
- Liquid upon instillation ( solution/suspension)
-Visco-elastic gel in cul-de-sac
- Increased precorneal residence time
 Diclofenac potassium
-Non Steroidal Anti-inflammatory Drug (NSAID)
-Treatment of miosis, post operative inflammation in cataract
surgery.

3. OBJECTIVE
 The objective of this study was to develope an ophthalmic insitu gel of
diclofenac potassium and to carry out evaluation tests to identify the
most ideal formulation.
Materials
 Diclofenac Potassium (gift sample: Novartis India Pvt. Ltd, Mumbai)
 Sodium Alginate (Loba chemie Pvt Ltd Mumbai)
 Hydroxy propyl methyl cellulose (HPMC) (Finar chemicals, Ahmadabad)
 D-Mannitol (Merck Ltd ,New Delhi)
 All other chemicals used were of AR grade.

4. METHODS
1.Compatibility studies b/w drug and polymers were carried out by Fourier Transform
Infrared spectroscopic technique using KB disc method.
2. Preparation of sodium alginate and HPMC solution : Batch-A : polymers were
weighed and powdered, added to phosphate buffer (pH-7) , rotated at 4000 rpm. Batch-
B: polymers added to acetate buffer, pH-5
3. Preparation of Drug polymer mixture: Homogenous solution of drug-polymer
mixture was prepared by continuous stirring followed by addition of mannitol and
cterimide.
• Fabrication of Ophthalmic Solution

5. Formulatio
n Code
Diclofenac
Potassium
(%w/v)
Sodium
alginate(%
w/v)
HPMC
(% w/v)
Mannitol
(%w/v)
Cetrimide
(%w/v)
A1 0.05 0.5 0.2 5.0 0.1
A2 0.05 1.0 0.2 5.0 0.1
A3 0.05 1.5 0.2 5.0 0.1
A4 0.05 2.0 0.2 5.0 0.1
A5 0.05 2.5 0.2 5.0 0.1
B1 0.05 0.5 0.2 5.0 0.1
B2 0.05 1.0 0.2 5.0 0.1
B3 0.05 1.5 0.2 5.0 0.1
B4 0.05 2.0 0.2 5.0 0.1
B5 0.05 2.5 0.2 5.0 0.1
Table No:1 Formulation Chart for the Ophthalmic Solution

6. EVALUATION OF OPHTHALMIC SOLUTIONS
1. Test for Clarity : Tested against black & white background.
2. pH detection : pH was determined using digital pH meter.
3. Sterility testing : Direct inoculation technique, detection of bacteria and
fungi was done using sterile fluid thioglycolate and soya bean casein digest
media respectively.
4. Surface tension : of the formulation was determined by Stalagmometer by drop
count method.
5. Viscosity determination : Viscosity of formulated solution and gel was
determined by Brookfield DVE digital viscometer.
6. Drug content : UV spectrophotometry was used for drug content analysis

7. 7. Gel Characteristic studies : Apparatus - fabricated gelation cells ;
Chemicals - simulated tear fluid solution-A (sodium chloride 0.670 g, sodium
bicarbonate 0.200 g, calcium chloride dihydrate 0.008 g and distilled water sufficient to
make 100 g) & STF solution- B (bovine serum albumin 0.268g, lysozyme 0.268g, D-
glucose 0.15g, sodium chloride 0.65g and distilled water qs to100g)
8. In-vitro release study : Apparatus - cellophane membrane ;
Dissolution medium – STF (pH-7.4) ; added 1 ml sample, analyzed in UV
spectrometer at 281nm.
9. Release kinetics : data obtained was fitted to Zero order, Higuchi matrix, and Peppas
model. After comparing the r-values , the best-fit model was selected.
10 Stability studies : formulations were kept at 4◦C , 37◦C and 45◦C for a period of 90
days. Samples were analyzed for appearance, viscosity, pH, gelation, drug content in-
vitro drug release.

8. Results & Discussions
TEST RESULT
• Appearance and Clarity Clear & Transparent
• pH of the Formulation In the range of 4.5-7.4. Minimizes the discomfort and
irritation of cornea
• Sterility of the
Formulation
Growth of microorganism was within the limit and thus
the solutions were sterile.
• Surface tension Values were very close to the value of normal human
tears (43 dyne/cm)
, ensuring good spreading of the solutions to the cornea.
• Viscosity Increase in viscosity was achieved . Formulae having the
composition of 2.5% w/v of Sodium alginate and 0.2%
w/v of HPMC was found to exhibit satisfactory results.
• Gelation studies Alginates at higher concentrations (1.5%-2.5%) showed
instantaneous gelation.

9. Continued..
• Drug Content
Drug
content of all the formulation was found in the range of
0.045 to 0.048.
• In-vitro release study
A-5 showed better
sustaining effect amongst all the formulations, it
showed 82.75% release in 10 hours.
• Release kinetics Studies All the formulations
followed Higuchi’s order release Kinetics
•Stability Studies A5 was found to be ideal formulation and have adequate
shelf-life.

10. Formulation
Identity
pH * Surface
tension(dynes/c
m)*
Viscosity(cps)* Drug
Content(gm)*
A2 7.4 43.71±0.413 15.93±0.4 0.0456±0.141
A3 7.4 44.76±0.382 17.1±0.21 0.0468±0.152
A4 7.4 44.95±0.267 19.9±0.25 0.0477±0.178
A5 7.4 43.16±0.289 21.6±0.09 0.0485±0.098
B1 7.4 42.23±0.413 11.9±0.16 0.0454±0.182
B5 7.4 44.94±0.398 20.2±0.24 0.0478±0.214
Table No:-2 Physicochemical Evaluation parameters of the formulations
* Three observations ± SD.

11. Table No:3 Percentage Drug Release Profile of Comparable Formulations

12. Figure No-1: Percentage Drug Release from Comparable Ophthalmic
Dosage forms.

13. Conclusion
•Diclofenac potassium was successfully formulated as an insitu gelling
system for ocular drug delivery in a sustained manner.
•Formulation A-5 containing polymer concentration about 2.5% showed a
compatible higher sustained release with better release pattern of drug.
•The samples showed no significant changes during the period of 90 days and
were stable. .

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