Development and in Vitro Evaluation of a Novel Multiparticulate Matrix Controlled Release Formulation of Theophylline

Abstract

A novel multiparticulate matrix controlled release preparation of theophylline was formulated and evaluated in-vitro. The preparation which consisted of spherical drug pellets in a size range of 1.18-1.70 mm diameter was produced using an extrusion-spheronisation technique. The drug was embedded in a mixture of nonsoluble matrix materials forming the pellets to control the drug release. For this purpose, microcrystalline cellulose (MCC) and its mixture with glyceryl monostearate (GMS) were evaluated. When microcrystalline cellulose was used alone, the drug release was not sufficiently sustained and was essentially complete within 6 hours. However, incorporation of glyceryl monostearate significantly retarded the rate of drug release. Moreover, the rate of drug release could be readily modified in a predictable manner by varying the amount of glyceryl monostearate. The rate of the drug release was relatively insensitive to changes in the drug to matrix ratio. Drying of the drug pellets at temperatures below the melting point of glyceryl monostearate (approximately 57°C) has no effect on the rate of drug release. In addition, the rate of drug release was found to be stable after storage for 6 months and was essentially independent of pH and agitation rate.