POST-GRADUATE STUDENTS

Among various approaches to acquire modified drug release, the use of polymers such as chitosan and its derivative, N-trimethyl chitosan chloride (TMC), in drug delivery systems hold special promise to achieve the desirable drug delivery requirements. Favourable characteristics like their non-toxic properties, bio-adhesiveness and biodegradability make these polysaccharides good candidates for use in safe and effective drug delivery devices. Chitosan has found numerous applications as a pharmaceutical excipient in drug delivery systems, including that of absorption enhancer for poorly absorbable, hydrophilic and/or macromolecular drugs. Cross-linking of chitosan molecules by means of oppositely charged ions leads to polymer matrix formation with decreased hydrophilic and subsequent modified drug release properties. Caco-2 cell monolayers have become a widely used in vitro model for the determination and screening of the intestinal transport of pharmaceutical compounds. These adenocarcinoma cells are grown on filter inserts and placed in wells that offer a two-chamber system with the possibility to monitor the movement of a drug from the apical to the basolateral side as a function of time. In this study ibuprofen was incorporated as a model drug into cross-linked polymer microparticulate systems consisting of chitosan alone, chitosan in combination with TMC and chitosan in combination with cetostearyl alcohol (CSA). The microparticles were prepared by screening a chitosan paste through a sieve and dropping these granules into a cross-linker solution. Melted CSA was added to two batches of microparticles of which one was compressed into slugs after which it was granulated again and the other batch was used as a mixture. These microparticulate systems were characterised by scanning electron microscopy (SEM) and in terms of their drug content. Their drug release properties were measured at three different pH values. The in vitro transport of ibuprofen released from these different chitosan microparticles was determined across Caco-2 cell monolayers.

Addition of TMC to the chitosan microparticles lead to an increase in ibuprofen release as compared to the control group, most probably due to better wettability and swellability. This is responsible for better dispersion of the microparticles in the dissolution medium with an increased surface area exposed to the dissolution medium. The chitosan microparticles in combination with CSA achieved a significant decrease in the drug release profile. This is probably caused by the barrier effect of the wax on the diffusion of the drug from the microparticles into the surrounding medium. The microparticles consisting of chitosan and those consisting of chitosan in combination with TMC showed the highest transport of the drug across intestinal epithelia. This is possibly due to the faster drug release, but interaction of the positively charged polymer molecules on the surface of the microparticles with the intestinal epithelial cells may have resulted in opening of the tight junctions. This opening of the tight junctions increases the transport of the drug across the intestinal epithelial cells. The method of microparticle preparation used in this study holds promise for up-scaling and resulted in modified release microparticulate drug delivery systems. The excipients used in combination with chitosan indicated potential for specific applications such as a slow down in drug release or an increase in drug transport across intestinal epithelia. The results obtained from this study contribute towards the development of an optimum microparticulate drug delivery system.