RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGLORE, KARNATAKA.

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the Candidate : Abdul Malik P.H

&Address S/O Hyderali V.T,

Poolakkal (House),

Parappanpoyil (Post),

Thamarasseri,

Calicut, Kerala, 673573.

2. Name of the Guide : Dr. K.Gowthamarajan

Professor & H O D Pharmaceutics,

Department of Pharmaceutics,

Bharathi College of pharmacy,

Bharathi Nagara, Mandya-571422.

3. Name of the Institute : Bharathi college of pharmacy,

Bharathi Nagara,

Mandya-571422

4. Course of the Study : Master of Pharmacy (Pharmaceutics)

5. Date of Admission : June-2007

6. Title of the Topic : Formulation and Evaluation of

Ocular In-situ Gel Drug Delivery System.

7. Brief Resume of the Intended Work:

7.1 General Discussion

Most commonly available ophthalmic preparation is eye drops and ointments. But the preparations when instilled in to the cul-de sac are rapidly drained away from the ocular cavity due to the tear flow and lachrymal nasal drainage. Only small amount is available for its therapeutic effect resulting in frequent dosing1. When a drug solution as dropped in to the eye, effective tear drainage and blinking results in 10-fold reduction of drug concentration in 4-20 minutes2.

The limited permeability of the cornea contributes to low absorption of ocular drugs. Due to tear drainage, most of the administered dose is absorbed via the nasal-lachrymal duct to the GI tract, leading to side effect, the rapid elimination of the administered eye drops often results in short duration of the therapeutic regimen necessary2, 3.

Ocular therapy could be significantly improved if the pre-corneal residence time of drugs could be increased, several new preparations have been developed for ophthalmic use not only prolong the contact time of the vehicle at ocular surface, but also to slow down the elimination of the drugs2, 3.

This problem can be overcome by using In-situ gel forming ophthalmic drug delivery systems prepared from polymers that exhibit reversible phase transition and pseudo-plastic behavior to minimize interference with blinking2.

7.2 Review of Literature

1. Shymala,B., et al.,2005. Prepared for the study of various ocular delivery systems and their characteristics, advantages and limitation of each system1.

2. Srividya,B., et al.,2001. Prepared “sustained ophthalmic delivery of ofloxacin from a pH triggered In-situ gelling system”, using poly acrylic acid (carbopol 940) and Hydroxy Propyl Methyl Cellulose (HPMC, Methocel E 50 LV). The developed formulation was therapeutically efficacious, stable, and nonirritant and provided sustained release of the drug over 8-hour period2.

3. Thilekk,K.M.,et al.,2005. Formulated “pH –induced In-situ gelling system of Indomethacin for sustained ocular delivery” using carbopol 974 P and HPMC. The enhanced therapeutic efficacy and sustained release of Indomethacin over 8-hour period in vitro make them an excellent candidate for In-situ gelling ocular delivery system3.

4. Yasmin Sultana,et al.,2006. Reported Evaluation of carbopol-Methyl cellulose based sustained-released ocular delivery system for pefloxacin mesylate using rabbit eye model. The results demonstrated that the carbopol/methyl cellulose mixture could be used by an In-situ gelling vehicle to enhance the ocular bioavailability of pefloxacin mesylate4.

5. Miyazaski,S.,et al.,2001. Prepared “In-situ gelling xyloglucan formulation for sustained release ocular delivery of pilocarpine Hcl”, using aqueous solution of an enzyme degraded xylogucan polysaccharide sustained release of pilocarpine was observed with all gels, the duration of mitotic response increasing with increase of xyloglucan concentration5.

6. Naseem,A.C.,et al.,2002. Developed “preparation of In-situ forming ophthalmic gels of ciprofloxacin Hcl for the treatment of Bacterial conjunctivitis: In vitro and In vivo studies”, using the phase transition properties of HPMC (K15M grade) and carbopol 934. Better improvement in artificially induced bacterial conjunctivitis in rabbit eyes was observed animals treated with the sol-to-gel system compared with marketed eye drops.

7.3 Scope of the Study

Ocular therapy could be significantly improved if the pre-corneal residence time of drugs could be increased, several new preparations have been developed for ophthalmic use not only prolong the contact time of the vehicle at ocular surface, but also to slow down the elimination of the drugs.

Such as inserts and ointments, were considered, these dosage forms have proven to be long duration and able to substantially modify drug bioavailability compared to their solution dosage form counterparts. However, these dosage forms present some disadvantages such as blurred vision and noncompliance.

This problem can be overcome by using In-situ gel forming ophthalmic drug delivery systems prepared from polymers that exhibit reversible phase transition and pseudo-plastic behavior to minimize interference with blinking.

Such system can be formulated as liquid dosage form suitable for administration by instillation in to the eye, which upon exposure to the eye, shift to the gel phase depends upon physiological pH condition of eye, temperature and ionic strength. The gel phase has a higher viscosity thus increasing the pre-corneal residence. The prolonged residence time of gel formed In-situ along with its ability, to release drug in a sustain manner will assist in enhancing the bioavailability of the instilled drug and improve patient compliance2, 3.

7.4 Objective of the Study

Hence, the present study to make an attempt to better residence time, enhanced bioavailability and improved patient compliance. Based on the objective the plan of the works is as follows.

1. Pre formulation studies

2. Preparation of In-situ gel

3. Evaluation of In-situ gel

4. Animal studies

8. Material and Methods:

Materials:

Polymers : Carbopol, Hydroxy Propyl Methyl Cellulose (HPMC),

Methyl Cellulose (MC), Chitosan, gellan gum etc...

Drugs : Anti-inflammatory, anti-infective or anti-allergic drug.

Other ingredients : Disodium edentate, benzalkonium chloride, propelene glycol, potassium dihydrogen orthophosphate, purified water etc…

Methods:

The following methods can be used for the preparation of the In-situ gel system.

1. Pre Formulation Studies:

a)  Solubility

b)  Dissolution

c)  Partition coefficient

d)  Rheological studies

e)  Stability studies

2. Preparation of In-Situ Gel System:

a) pH method

b) Temperature method

c) Ionic strength method

3. Evaluation Parameter:

a) In-vitro gelling capacity

b) Rheological studies

c) In-vitro release of In-situ gel forming system

4. In-vivo animal studies

9.  References

1. Shymala, B.P., Lakshmi, K.,and Harish, C.G. 2005. Topical ocular drug delivery. Indian Journal of Pharmaceutical Science, 67 (3), 404-408.

2. Sri Vidya, B., Cardoza, R.M., Amin, P.D. 2001. Sustain ophthalmic delivery of ofloxacin from a pH triggered In-situ gelling system, Journal of controlled release, 73 (2-3), 205-211.

3. Thilek,K.M., Bharathi, D., Bhalasubramanium, J., Kant, S., and J.K pundit. 2005. pH induced In-situ gelling of indomethacin for sustained ocular delivery, Indian Journal of Pharmaceutical Science, 67(3), 327-333.

4. Yasmin,S., Aqil, M., Ali, A., Jafar,S. 2006. Evaluation of carbopol methyl cellulose based sustained release ocular delivery system for pefloxacin mesylate using rabbit eye model, Pharmaceutical Development Technology, 11 (3), 313-319.

5. Miyazaski, S.,Suzuki, s.,Kawasaki, N., Endo, K.,Takhashi, A.,Altwood, D 2001. In-situ gelling formulation for sustained release ocular delivery of pilocarpine Hcl”,International Journal of Pharmaceutical Science, 229(1-2), 29-36.

6. Naseem, A.C., Kanchan, K., Asgar, A. 2002. Preparation of In-situ forming ophthalmic gels of ciprofloxacin Hcl for the treatment of Bacterial conjunctivitis: In vitro and In vivo studies, Journal of Pharmaceutical Science, 92 (2), 407-413.

7. Rao, K.P., and Bhushetti, S.S., 2006. Phase transition system of timolol maleate for Glaucoma treatment: Prolonged acting ocular delivery in Glaucoma therapy, Indian Drugs, 43 (11), 909-913.

8. Kumar, S., Hmmelstain,K.J. 1995. Modification of In-situ gelling behavior of carbopol solutions by HPMC, Journal of Pharmaceutical Science, 85 (3), 344-348.

9. Remington The Science And Practice Of Pharmacy, 21st edition, vol.1 pp 850-870, Lippincott, Williams and Wilkins.

10. Herbert, A., Liberman, Martin. M.Rieger and Gilbert.S.Banker., Pharmaceutical Dosage Form: Disperse System, 2nd edition, vol.2, pp 357-397, Marcel Dekker, Inc. 270, Madidison Avenue, New york.

11. Yie, W, Chein., Novel Drug Delivery System, 2nd revised edition, Marcel Dekker Inc. New York pp 269-300.

10. Source of Data:

1. Library: Bharathi College of Pharmacy

2. e-library: Bharathi College of Pharmacy

11. Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so please describe.

-Yes-

Ocular therapeutics efficacy will be perform in rabbit like eye irritation test, Ocular Retention Time (ORT), etc.

11.1. Has ethical clearance has been obtained from your institution in case 11?

-Yes-

Waiting for approval from ethical committee.

Or

Work to be carried out from ethical committee approved college.

12. Signature of the Candidate :

13. Remarks of the Guide :

Signature:

14. Remarks of Head of the Department :

Signature:

15. Remarks of the Principal :

Signature:

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