Evaluation of Controlled Release Theophylline Microspheres Prepared with Cellulose Acetate Using Solvent Evaporation Method

Abstract

Purpose: To formulate theophylline microspheres with cellulose acetate using solvent evaporation method and evaluate the effect of various processing factors on their characteristics. Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer - cellulose acetate - by an emulsion solvent evaporation technique using an acetone/liquid paraffin system containing Span 80 as a surfactant. The effect of processing factors, e.g., varying drug/polymer ratio (1:1, 1:2, 1:3) and temperature (10 and 35 °C) on microsphere characteristics and drug release were examined. Similarly, microspheres with a drug/polymer ratio of 1:3 incorporating Span 20 were also also prepared and evaluated. Results: The microspheres were white, free-flowing and spherical. The yield varied from 73.0 to 87.5 % while entrapment efficiency was in the region of 71.8 to 92.4 %. High drug/polymer ratio, Span 80 (surfactant) and processing temperature between 10 and 30 °C produced formulations with better drug entrapment efficiency. High drug/polymer ratio, low processing temperature and low HLB value of surfactant enhanced the sustained drug release characteristics of the microspheres. Conclusion: The combination of three suitable factors - Span mixture (with HLB value of 4.3), processing temperature of 10 °C and drug/polymer ratio of 1:3 - produced a suitable controlled release theophilline microsphere formulation which could be effective for the management of asthma.