Application of binary polymer system in drug release rate modulation. 2. Influence of formulation variables and...

The significance of factors such as drug solubility, polymer molecular weight, drug loading dose, compression force, and hydrodynamic conditions on drug release from a swellable hydrophilic delivery system was investigated. Hydroxypropyl methylcellulose (HPMC) and pectin were major polymeric constituents of the delivery system. Nifedipine, prednisolone, theophylline anhydrous, and diltiazem hydrochloride with solubilities of < 0.001%, <0.1%, <1%, and >50%, respectively, were used as drug models. Results show that changes in pectin:HPMC ratios, HPMC molecular weight, and hydrodynamic conditions exert notable influences on release rate and release duration from the designed system. In the case of prednisolone, drug loading up to 30% (w/w) of the matrix composition (pectin:HPMC K4M; 3:6) had no effect on zero-order release kinetics, and the delivery system was insensitive to changes in compression force (2000 to 5000 lb). For nifedipine, theophylline, and diltiazem, determination of mean dissolution time (MDT) for 50 and 80% drug release provided accurate information on release behavior. The dominating effect of matrix composition over variations in drug solubilities in controlling drug release from the delivery system was evident from similarities in dissolution profiles. It is further shown that hydrodynamic stress and intensity of fluid flow causes greater attrition at the swollen periphery and is responsible for dramatic increases in release rates. 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 potential of the delivery system is discussed.