Optimum heat treatment conditions for masking the bitterness of the clarithromycin wax matrix

Abstract

The effects of the contents of aminoalkyl methacrylate copolymer E (AMCE) in a wax matrix on the mechanism of polymorphic transformation of glyceryl monostearate (GM) were clarified by evaluating the enthalpy change defined as 1.51 (ΔH1-ΔH2)/ΔH2, where ΔH1 and ΔH2 denote the enthalpies in the first and second thermal analyses, respectively. Using this value, K1, the rate constant of transformation from α-form to β′-form, and K2, the rate constant of transformation from β′-form to β-form, could be obtained. As the ratio of AMCE increased, K2 increased, but a minimum point existed for K1. K1 was always larger than K2, but gradually approached K2 as the ratio of AMCE increased. The optimum temperature for the transformation of GM was 50°C, at which the enthalpy change was maximum. To prepare the wax matrix preparation of clarithromycin (CAM), we considered 40°C the optimum treatment temperature for the transformation of GM in a CAM wax matrix compounded from CAM, GM and AMCE, since the matrices were mutually welded at above 45°C during the spray congealing process. Although K1 and K2 were almost the same at 40°C, the rate of transformation was accelerated by tumbling. By applying the tumbling that accelerated the transformation of GM in a CAM wax matrix, almost all of the α-form disappeared, and the release of CAM from the wax matrix diminished when the enthalpy change was more than 0.8. © 2003 Pharmaceutical Society of Japan.