APPLICATION OF THERMODYNAMIC ACTIVATION PARAMETERS FOR THE ASSESSMENTOF DRUG-RELEASE FROM INERT, HETEROGENEOUS MATRICES

Sustained-release tablet matrices of ketoprofen (10%) were prepared us ing Dynasan (50%), polyvinylpyrrolidone and lactose (40%). Three diffe rent methods of preparation were used for the powders from which the m atrices were compressed. physical mixtures, binary drug/polyvinylpyrro lidone coprecipitates mixed with Dynasan and lactose, and drug/polyvin ylpyrrolidone/Dynasan ternary coprecipitates mixed with lactose. Three concentrations of polyvinylpyrrolidone (10, 20 and 30% w/w) were trie d in each of the previous methods. Drug release was performed from con stant tablet surface in 0.1 N hydrochloride and buffer (pH 7.2) dissol ution media at four temperatures, ranging from 25 to 40 degrees C. The drug release in the buffer medium was higher than that in the acid me dium and was in the following order: binary coprecipitate > ternary co precipitate > physical mixture. In addition, the drug release rate was improved by increasing polyvinylpyrrolidone concentrations. The relea se data fit the square root of time model from which the apparent diff usion constants were calculated. Thermodynamic functions were calculat ed from the apparent diffusion constants using a modified Arrhenius eq uation. From the free energy/enthalpy compensation analysis, it was co ncluded that the release mechanism of ketoprofen in an acidic medium w as different from that in a buffer medium. In addition, the drug relea se in any of the media followed two mechanisms, one for the physical m ixtures and the other for the binary and ternary systems (with the exc eption of the binary coprecipitate containing 30% polyvinylpyrrolidone in an acid medium). There was a good correlation between the release rate and thermodynamic parameters concerning the effect of the method of preparation and polyvinylpyrrolidone concentrations.