APPLICATION OF BINARY POLYMER SYSTEM IN DRUG-RELEASE RATE MODULATION .2. INFLUENCE OF FORMULATION VARIABLES AND HYDRODYNAMIC CONDITIONS ON RELEASE KINETICS

The significance of factors such as drug solubility, polymer molecular weight, drug loading dose, compression force, and hydrodynamic condit ions on drug release from a swellable hydrophilic delivery system was investigated. Hydroxypropyl methylcellulose (HPMC) and pectin were maj or polymeric constituents of the delivery system. Nifedipine, predniso lone, theophylline anhydrous, and diltiazem hydrochloride with solubil ities of <0.001%, <0.1%, <1%, and >50%, respectively, were used as dru g models. Results show that changes in pectin:HPMC ratios, HPMC molecu lar weight, and hydrodynamic conditions exert notable influences on re lease rate and release duration from the designed system. In the case of prednisolone, drug loading up to 30% (w/w) of the matrix compositio n (pectin:HPMC K4M; 3:6) had no effect on zero-order release kinetics, and the delivery system was insensitive to changes in compression for ce (2000 to 5000 lb). For nifedipine, theophylline, and diltiazem, det ermination of mean dissolution time (MDT) for 50 and 80% drug release provided accurate information on release behavior. The dominating effe ct of matrix composition over variations in drug solubilities in contr olling drug release from the delivery system was evident from similari ties in dissolution profiles. It is further shown that hydrodynamic st ress and intensity of fluid flow causes greater attrition at the swoll en periphery and is responsible for dramatic increases in release rate s. This latter observation confirms that the mechanism of drug release from this swellable system is erosion dependent. Influence of polymer molecular weight and drug solubility on release kinetics and the pote ntial of the delivery system is discussed.