Development and characterization of polymeric drug delivery systems prepared by hot-melt extrusion: Solubility, stability, bioadhesion and mechanical studies

The purpose of the research is to develop and characterize formulations prepared via hot-melt extrusion (HME). Fenofibrate, promethazine hydrochloride (PMZ), and carbamazepine (CBZ) were selected as model drugs. The formulation projects are as follows:;✓ Enhancement of dissolution and stability of fenofibrate in low molecular weight hydroxypropylcellulose (LMW HPC) matrices produced by HME. Percent drug loading had a significant effect on the extrudability of the formulations. Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0.05). Incorporation of sugars within the formulation further increased the fenofibrate release rates. Fenofibrate is prone to recrystallization due to its low Tg. Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates. Immediate-release fenofibrate tablets were successfully developed with Kollidon RTM VA 64. Complete drug release was achieved within 5 min, which was comparable to that of a currently marketed formulation. Moreover, the tablet formulation was chemically and physically stable, and the formulation exhibited an unchanged drug release profile after 6-month storage at 40°C/75% RH. This study verified that HME is an efficient processing method and a commercially viable option to enhance the dissolution of fenofibrate.;✓ Formulation and in vitro evaluation of a sustained release system of promethazine hydrochloride using EudragitRTM and Poly (Ethylene Oxide) blends. The release of PMZ from the matrices was influenced by the type and level of the plasticizer system investigated. These findings emphasize the importance of selecting an appropriate plasticizer system in order to obtain a desired release profile.;✓Development and evaluation of a hot-melt extruded oral delivery system of carbamazepine prepared with polymeric blend of KollidonRTM VA 64 and KlucelRTM EF. Blends of Klucel RTM EF and KollidonRTM VA 64 tailored the release of CBZ from the hot-melt extruded systems. The melt-extrusion temperature profile is a critical parameter in formulation of hot-melt extruded delivery systems of CBZ. CBZ was shown to be chemically and physically stable after storage for the duration of this study.