Determination of optimum processing temperature for transformation of glyceryl monostearate

Abstract

The purpose of this study was to clarify the mechanism of transformation from α-form to β-form via β′-form of glyceryl monostearate (GM) and to determine the optimum conditions of heat-treatment for physically stabilizing GM in a pharmaceutical formulation. Thermal analysis repeated twice using a differential scanning calorimeter (DSC) were performed on mixtures of two crystal forms. In the first run (enthalpy of melting: ΔH1), two endothermic peaks of α-form and β-form were observed. However, in the second run (enthalpy of melting: ΔH2), only the endothermic peak of the α-form was observed. From a strong correlation observed between the β-form content in the mixture of α-form and β-form and the enthalpy change, (ΔH1-ΔH 2)/ΔH2, β-form content was expressed as a function of the enthalpy change. Using this relation, the stable β-form content during the heat-treatment could be determined, and the maximum β-form content was obtained when the heat-treatment was carried out at 50°C. An inflection point existed in the time course of transformation of α-form to β-form. It was assumed that almost all of α-form transformed to β′-form at this point, and that subsequently only transformation from β′-form to β-form occurred. Based on this aspect, the transformation rate equations were derived as consecutive reaction. Experimental data coincided well with the theoretical curve. In conclusion, GM was transformed in the consecutive reaction, and 50°C was the optimum heat-treatment temperature for transforming GM from the α-form to the stable β-form. © 2002 Pharmaceutical Society of Japan.