Tablet shapes and in vitro evaluation of coated hydrophilic matrix tablets, Novel mupirocin formulations, Non-acidic enteric coating of omeprazole, and, Novel hot -melt coating process.

摘要

This dissertation is comprised of four distinct formulation sections, which are described below:;A novel solid dosage formulation was investigated for achieving zero-order drug release profile by combining tablet shape design and tablet membrane film coating. Verapamil (model drug) was compressed into hydrophilic matrix tablet cores of flat-faced and bi-convex shape, which were encapsulated with membrane controlling film. The hydrophilic tablet core contained hydroxypropyl methylcellulose (HPMC) 15 LV, pectin, and AvecilRTM. The membrane film coating solution was comprised of deionized water, Opadry RTM, SureleaseRTM and talc. The combination of membrane film coating and tablet shape design was found to influence in vitro verapamil release profile towards the zero-order release demonstrated by the commercial Covera HSRTM (Pharmacia).;An alternative formulation for the commercial BactrobanRTM (Smithkline Beacham) ointment 2% was developed. Both the texture and consistency of the new ointment were comparable to the BactrobanRTM ointment. The new and the commercial formulations were found to be equivalent in drug release by the BauerKirby test. Mupirocin remained unstable in the new formulation. Mg2+ was added to help stabilize mupirocin and was shown to complex with mupirocin by nuclear magnetic resonance (NMR). The modified formulation including Mg2+ however failed to stabilize mupirocin. The stability assay results showed an average of 67.2% mupirocin recovery along with 25.2% degradation products.;A generic omeprazole formulation was developed, which was comprised of nonpareil core, omeprazole matrix layer, and an enteric locating layer of ammoniated hydroxypropyl methylcellulose phthalate (HPMCP) 55S. The new formulation was gastro-resistant in protecting against omeprazole degradation for up to 2 h, but failed to dissolve as rapidly as the commercial PrilosecRTM (Astra Merk) in simulated intestinal fluid. The addition of expotab RTM to the enteric coating layer failed to improve omeprazole dissolution rate.;A novel hot-melt coating methodology utilizing direct blending technique has been developed. The processing steps for the direct blending hot-melt coating are: (a) Hot-melt system preparation; (b) Dispersion/dissolution of the active ingredient(s) in the hot-melt system; (c) Pre-heating of the coating substrate; and (d) Cooling and congealing of the hot-melt on substrate surface. Immunogenic effect was observed in mice administered with enteric-coated ragweed pollen extract (RPE) alpha fraction by the hot-melt coating encapsulation with direct blending method. The effect was not shown to be statistically significant.