Rajiv Gandhi University of Health Sciences, Karnataka



DESIGN AND CHARACTERIZATION OF

BIOADHESIVE IN-SITU GELLING OCULAR INSERTS

SYNOPSIS FOR

M.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

BY

P.BALA SUBRAMANYAM

I M.PHARM (2009-10)

Department of Pharmaceutics

M.S. Ramaiah College of Pharmacy

BANGALORE-560 054.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECT FOR

P.G DISSERTATION

| | | |

|1. | |Mr. P.BALA SUBRAMANYAM |

| |NAME OF THE CANDIDATE AND |H.No:6/234, MAIN ROAD |

| |ADDRESS ( IN BLOCK LETTERS) |KANIGIRI |

| | |PRAKASAM DISTRICT |

| | |PINCODE- 523230 |

| | |ANDHRA PRADESH. |

| | | |

|2. |NAME OF THE INSTITUTION |M.S RAMAIAH COLLEGE OF PHARMACY |

| | |M.S.R.NAGAR, M.S.R.I.T. POST |

| | |MATHIKERE |

| | |BANGALORE –560 054. |

| | | |

|3. |COURSE OF STUDY AND SUBJECT |M.PHARM. |

| | | |

| | |PHARMACEUTICS |

| | | |

|4. |DATE OF ADMISSION TO COURSE |30th NOVEMBER 2009 |

| | |

|5. | |

| |TITLE OF THE TOPIC |

| | |

| |DESIGN AND CHARACTERIZATION OF BIOADHESIVE |

| |IN-SITU GELLING OCULAR INSERTS |

| | |

6. BRIEF RESUME OF THE INTENDED WORK

1. NEED FOR THE STUDY

The conventional ocular delivery systems which are eye solutions, eye suspensions, eye ointments are used to treat ocular infections. Most of these treatments call for the topical administration of the ophthalmically active drugs to the tissues around the ocular activity. But when they are instilled into the cul-de-sac of the eye, they get rapidly drained away from the pre-corneal cavity by lacrimo-nasal drainage1 which results in poor bioavailability due to decreased pre-corneal contact time. For this reason concentrated solutions and frequent dosing are required for the instillation to achieve an adequate level of therapeutic effect.

Several polymeric systems have been used to fabricate ocular inserts for better ocular bioavailability and retention to drug of which gelling systems have shown advantages of convenient administration and increased contact time based on mucoadhesive concept.2 These systems consist of polymers that exhibit sol- to-gel phase transitions due to change in specific physico-chemical parameter (pH, temperature) in their environment of cul-de-sac. Depending on the method employed to cause sol-to-gel phase transition on the eye surface, the following three types of systems are recognized: pH triggered system, temperature dependant system3 and ion activated system.

Ophthalmic inserts are defined as sterile preparations with a solid or semisolid consistency for topical or systemic therapy. The main objective of the ophthalmic inserts is to increase the contact time between the preparation and the conjunctival tissue to ensure a sustained release. Some of the merits of the ocular inserts and in-situ ophthalmic gelling systems are:

➢ Increased contact time and thus improved bioavailability.

➢ Possibility of providing a prolonged drug release and thus a better efficacy.

➢ Reduction of systemic side effects and thus reduced adverse effects.

➢ Reduction of the number of administrations and thus better patient compliance4.

Owing to the above factors, in the present study the concept of in-situ gelling with ocular insert formulation is used to extend the drug release of antibacterial agent for the treatment of ophthalmic infections like sub acute conjunctivitis, bacterial keratitis and keratoconjunctivitis etc.

6.2 REVIEW OF LITERATURE

➢ The basic concept of ocular inserts as drug delivery system and the types of devices like soluble ocular drug insert (SODI), ocusert, collagen shields, ocufit, minidisk and new ophthalmic delivery system (NODS) with special attention to biological or clinical performances and potential for future applications and developments have been discussed.1

➢ The polymeric ocular inserts of Gatifloxacin sesquehydrate using sodium alginate and chitosan with glycerin as plasticizer by solvent casting method was prepared. The ocular inserts were investigated for physicochemical properties, mechanical strength, swelling index, and bio-adhesion parameters.2

➢ The formulation and evaluation of an ophthalmic delivery system of an antibacterial agent ciprofloxacin based on the concepts of pH-triggered in-situ gelation, thermo reversible gelation and Ion-activated system was discussed.3

➢ Several polymeric systems to fabricate ocular inserts for better ocular bioavailability and retention to drug with an objective to develop ocular inserts of pefloxacin and evaluate their potential for controlled ocular delivery was studied.4

➢ The reservoir type ocular inserts was fabricated using sodium alginate containing ciprofloxacin hydrochloride as the core was sandwiched between the Eudragit and/or polyvinyl acetate films. The formulations were evaluated for in-vitro release rate studies, microbial efficacy, in-vivo release studies, efficacy against induced bacterial conjunctivitis in rabbit’s eyes, concentration in the aqueous humor and stability studies as per the International Conference on Harmonization guidelines were reported.5

➢ The ocular inserts with prolonged release of drug and minimum swelling within cul-de-sac using ofloxacin as a model drug and hydroxy propyl methyl cellulose, methyl cellulose, poly vinyl pyrrolidone and poly vinyl alcohol as polymers with a purpose to deliver the drug in zero order kinetics by solvent casting technique was reported.6

➢ The effects of chitosan hydrochloride on in-vitro release of ofloxacin from mucoadhesive erodible ocular inserts and on the relevant ocular pharmacokinetics have been studied.7

➢ The ophthalmic gels of fluconazole using the cold method along with thermo reversible poloxamer 407 and different mucoadhesive polymers such as hydroxy ethyl cellulose, hydroxy propyl methyl cellulose and polyvinyl pyrrolidone were formulated and evaluation of physical parameters and in-vitro permeation through a sheep's corneal membrane were reported.8

➢ The controlled release ophthalmic delivery systems for ciprofloxacin in an attempt to prolong the effect and improve its ocular bioavailability using carbopol and alginates polymers to confer gelation properties to the formulations were reported.9

➢ The rheological properties, precorneal resident time, in-vitro drug release, in-vivo resident properties and improved ocular bioavailability of Vitamin-B12 using Pluronic-g-poly(acrylic acid) copolymers were investigated.10

6.3 AIMS AND OBJECTIVES OF THE STUDY

➢ To develop an in-situ gelling Ocular inserts containing an anti-infective drug using bio-adhesive polymers like chitosan, hydroxy propyl cellulose , hydroxy propyl methyl cellulose etc with temperature dependent, pH triggered or ion-activated polymers like pluronics, tetronics, carbopol, gellan, sodium alginate and Gelrite etc.

➢ To study the physico-chemical evaluation of in-situ gels and ocular inserts.

➢ To study the influence of bio-adhesive polymers on drug release kinetics from the formulations.

➢ Stability studies of the optimized as per ICH guidelines.

7. MATERIALS AND METHODS

7.1 SOURCE OF DATA

1. Library: M.S.Ramaiah College of Pharmacy.

2. e-library: M.S.Ramaiah College of Pharmacy.

3. Official books (IP, BP and USP).

4. Internet.

5. RGUHS Library, Bangalore (J-Gate Helinet).

6. Micromedex® Health care series DIC: M.S.Ramaiah College of Pharmacy.

7. International and National Pharmaceutical Journals.

8. Lab based studies.

MATERIALS

1. Classical anti-bacterial drug will be selected for the study

2. Other polymers, excipients and reagents used will be of L.R grade and all the solvents

used will be of A.R. grade procured from reliable sources.

7.2 METHODS OF COLLECTION OF DATA

Data will be collected from the experimental work which includes:

1. PRE-LABORATORY WORK

The drug, solvents and excipients required for the formulation and evaluation of the in-situ gelling ocular inserts will be procured from the reputed chemical suppliers like Merck, Ranbaxy, Qualigens and Himedia etc.

2. LABORATORY WORK

a. Pre-formulation studies involving the bland in-situ gelling Ophthalmic inserts will be made using different polymer blends in various ratios and combinations using techniques like mercury substrate method, glass plate method etc. and studied for its compatibility and stability.

b. Formulation of the in-situ gelling ophthalmic insert containing an anti-infective agent using the stabilized method.

c. Evaluation of the designed formulation like thickness of the insert, weight variation test, drug content, mechanical strength, drug-polymer compatibility studies, sterility test, in-vitro drug release studies11,13, comparative drug release profile between the optimized formulation and the conventional marketed product and the stability studies as per the ICH guidelines.12

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS TO BE CONDUCTED ON PATIENTS/ HUMANS/ ANIMALS? IF SO, PLEASE DESCRIBE BRIEFLY.

-NO-

7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?

-NOT APPLICABLE-

8. LIST OF REFERENCES

1. Divasi Gamani karthikeyan, Mithun Bhowmick, Vijay Prakash pandey, Jothivel, Nandakumar, Singaravel, Sengottuvelu, Sandeep sonkar, Thangavel Siva kumar. The concept of ocular inserts as drug delivery systems. Asian journal of pharmaceutics. 2008 Oct-Dec; 2(4):192-200.

2. Eaga Chandra Mohan, Jagan Mohan kandukuri, Venkateshan allenki. Preparation and evaluation of in-situ gels for ocular drug delivery. Journal of pharmacy research. 2009;2 (6):1089-1094.

3. Mishra D.N, Gilhotra R.M. Design and characterization of bio-adhesive in-situ gelling ocular inserts of gatifloxacin sequehydrate. Daru. 2008;16(1):1-8.

4. Harish N.M, Nirmal Mathew, R. Narayana charyulu and Prabhakara Prabhu. Improved bioavailability of Pefloxacin using controlled release ocular inserts. International Journal of Pharmaceutics. 2009 Nov-Dec;1(1):71-78.

5. Naseem A. Charoo, Kanchan Kohli, Asgar Ali, Areeg Anwer. Ophthalmic delivery of ciprofloxacin hydro chloride from different polymer formulations: In-vitro and in-vivo studies. Drug Development and Industrial Pharmacy. 2003;29(2):215-221.

6. Srinivas S. A, Hiremath S. P and Godbole A.M. Oflaxacin ocular inserts: Design, Formulation and Evaluation. Iranian Journal of Pharmacology and Therapeutics. 2006;5 (2):159-162.

7. G. Di colo, Y. Zambido, S. Burgalassi, A. Serafini, M.F.Saettone. Effect of chitosan on in-vitro release and ocular delivery of ofloxacin from erodible inserts based on Poly (ethylene oxide). International Journal of Pharmaceutics. 2002;248:115-122.

8. Indrajeet D. Gonjari, Avinash H. Hosmani, Amrit B. Karmarkar, Appa Saheb S. Godage, Sharad B. Kadam, Pandureng N. Dhabale. Formulation and evaluation of in-situ gelling thermo reversible mucoadhesive gel of Fluconazole. Drug Discovery and Therapeutics. 2009;3(1):6-9.

9. Raida S. Al-Kassas and Mona M. El- Khathib. Ophthalmic controlled release in-situ gelling systems for ciprofloxacin based on polymeric carriers. Drug Delivery. 2009;16 (3):145-152.

10. Wen-Dima, Hui xu, Shu-fangnie and wei-san-pan. Temperature- Responsive, pluronic- G-Poly (acrylic acid) co-polymers in-situ gels for ophthalmic drug delivery, rheology, in-vitro drug release and in-vivo resident property. Drug Development and Industrial Pharmacy. 2008;34:258-266.

11. Pandit J.K, Bharathi D, Srinitha A, Ridhurkar D.N, Singh S. Long acting ophthalmic formulation of indomethacin: Evaluation of alginate gel systems. Indian journal of pharmaceutical sciences. 2007 Jan-Feb;69(1):37-40.

12. Hitesh Gevariya, Abhay Dharamsi, Kundlik Girhepunje, Ranju pal. Once a day ocular inserts for sustain delivery of levofloxacin: Design, formulation and evaluation. . Asian journal of pharmaceutics. 2009 Oct-Dec;3(4):314-318.

13. Doijad R.C, Manvi F.V, Malleswara Rao V.S.N, Prajakta Alase. Sustained ophthalmic delivery of gatifloxacin from in-situ gelling system. Indian journal of pharmaceutical sciences. 2006 Nov-Dec;68(6):814-818.

| 9 |SIGNATURE OF THE CANDIDATE | |

| 10 |REMARKS OF THE GUIDE |Forwarded For Approval |

| |NAME AND DESIGNATION OF: | |

|11 | | |

| | |Dr. S.BHARATH, M.Pharm, Ph.D.,PDCR. |

|11.1 |GUIDE |Professor & Head |

| | |Dept. of Pharmaceutics |

| | |M.S.Ramaiah College of Pharmacy |

| | |BANGALORE –560 054. |

| |SIGNATURE | |

|11.2 | | |

|11.3 |CO-GUIDE |Not Applicable |

|11.4 |SIGNATURE |Not Applicable |

| | |Dr. S.BHARATH, M.Pharm., Ph.D., PDCR. |

|11.5 |HEAD OF THE DEPARTMENT |Professor & Head |

| | |Dept. of Pharmaceutics |

| | |M.S.Ramaiah College of Pharmacy |

| | |BANGALORE –560 054. |

| | | |

| | | |

| | | |

|11.6 | | |

| |SIGNATURE | |

| |12.1 REMARKS OF THE | |

|12 | |Recommended For Approval |

| |PRINCIPAL | |

| |12.2 SIGNATURE | |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download