Influence of Drug Solubility and Matrix Structure on Release Rate of Drugs from Wax Matrix Tablets

In order to elucidate individually the influence of drug solubility and the matrix structure on the drug release rate from a wax matrix tablet, the intrinsic dissolution rates of drugs and the release rates of several matrix tablets consisting of various proportions of drug and hydrogenated castor oil were measured for five drugs differing in solubility. From the theoretical modification of Higuchi's equation, the boundary retreat rate of the matrix tablet was expressed with two parameters : one parameter was a constant consisting of three physical quantities (diffusivity, solubility and density), and the other was the tortuosity representing the matrix structure. As the constant term in the modified Higuchi's equation was related to the intrinsic dissolution rate constant for every drig, it was found to be an index of the drug solubility in the matrix system. From this study, therefore, it is clear that boundary retreat rate constant, namely, the drug release rate constant form the matrix tablet, was in proportion to the solubility and in inverse proportion to the square root of tortuosity. The relation between the tortuosity and the void space (porosity) was well expressed by the proposed equation derived on the basis of the free volume theory (H. Yasuda and C. E. Lamaze, J. Polymer Sic., Part A-2, 9, 1537 (1971)). It was found that the tortuosity in the matrix tablets varied with the drug species even though the porosity was the same, and also the dependency of tortuosity on porosity varied. Further, it was determined that the dependency of tortuosity on porosity could be controlled by the addition of other materials.