MECHANICAL AND COMPRESSION CHARACTERIZATION OF PELLETES PREPARED BY EXTRUSION-SPHERONIZATION

Part 1 The first part concern the characterization of mechanical and compression properties of pellets prepared by extrusion-spheronization. Thirteen batches of pellets were prepared all in the same condition, using five materials (corn starch, α-lactose monohydrate, anhydrous dicalcium phosphate, peg 6000 and amidated pectin) plus microcrystalline cellulose as main binder, in fixed ratio, 75, 50 and 25% respect the cellulose amount. A further batch was prepared using only microcrystalline cellulose. A characterization program were carried out on the compression and mechanical properties of the starting materials, powder mixtures and pellets, the latter analysed either as single unit that during compression. Results showed as pellets compaction behaviour is strongly related to the properties of powder mixtures used for their preparation and it could be also derived from single components characteristics according with the ratio used. Diametrical compression tests and pellets images before and after such test enabled to link mixtures and pellets compaction behaviour, moreover these tests allowed to classify pellets as fragmenting and deforming. Despite the similar compaction mechanism mixtures and pellets behaved completely different in term of tablettability. A marked increase on surface area resulted crucial in order to obtain pellets tablets, as confirmed by the fragmenting batches results. All pellets classified as deforming seem suitable as core materials for the film coating application,in the preparation of multiparticulate controlled release tablets. They resist to the compaction process retaining their shape, so they represent good system in order the maintain the film integrity. All pellets classified as fragmenting pellets do not result useful as ''cushioning agents'' in multiparticulate controlled release tablets. Moreover the spheronization carried out on dense extrudate (as in this case) do not represent the best methodology for this purpose. Part 2 The second part, carried out at the school of pharmacy and chemistry, John Moore University (UK) under the supervision of Dr. M. Roberts, concerning the influence of hydro-ethanolic media on the aspirin release profiles from hypromellose matrices. Percent aspirin released increased with increasing levels of ethanol in the dissolution media, correlating with the drug's solubility, however,dose dumping of aspirin did not occur. An initial rapid release was observed in media comprising 40% ethanol. Release in these conditions was considered to be both erosion and diffusion-mediated, in contrast to the release in 0, 10, 20 and 30% ethanol media, where erosion-controlled release dominated. Image analysis of matrix swelling indicated a slower initial interaction between ethanol and hypromellose accounting for the initial rapid release. Cloud point studies suggested that ethanol retarded hydration of the polymer.