The purpose of this project was to fabricate biodegradable ophthalmic inserts for controlled delivery of pilocarpine and evaluate them by both in-vitro and in-vivo studies. Emphasis was placed on the use of an inexpensive material as a drug carrier and on the ease of fabrication of the device. Based on these criteria, absorbable gelatin was selected to fabricate a matrix system. Absorbable gelatin can be obtained by either thermal treatment or chemical crosslinking of gelatin. In the first part of this project, we fabricated an insert using Gelfoamᴿ, an absorbable gelatin sponge obtained by thermal treatment. A prolonged in-vitro release of pilocarpine from the device was achieved through pharmaceutical modification by embedding a retardant in the pores. The devices impregnated with polyethylene glycol monostearate (PMS) and cetyl esters wax (CEW) were found to be most effective. The in-vivo evaluation of the devices indicated that pharmaceutical modification of Gelfoamᴿ is an effective means of improving the biological activity of pilocarpine without altering the biodegradability of the biopolymer backbone. The CEW device produces a substantial improvement in drug bioavailability and an increase in the duration of biological effect over that from the two commercial formulations, the eyedrop and the gel. In the second part of the project, we fabricated absorbable gelatin inserts through chemical crosslinking of gelatin. The effect of selected fabrication variables on profiles of the in-vitro release of pilocarpine and the dynamic water uptake by the crosslinked gelatin devices was investigated. These results were further substantiated by the measurement of the degree of crosslinking of gelatin. The in-vivo study indicated that the modification of the structure of gelatin by crosslinking is another simple and effective way of improving bioavailability and extending the duration of effect of pilocarpine incorporated in the biopolymeric device. In addition, altering the degree of crosslinking of gelatin allows a variation of the biodegradation time of the polymer.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/185007 |
| Date | January 1990 |
| Creators | Nadkarni, Sreekant Raghuveer. |
| Contributors | Yalkowsky, Samuel H., Burke, Michael |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Dissertation-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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