Study of pharmaceutical solid dispersions by microthermal analysis.

Abstract

PURPOSE: The main objective of the study was to determine the ability of microthermal analysis (microTA) to assess the crystallinity of the drug in two noncommercial pharmaceutical solid dispersions. METHODS: Pure substances, physical mixes, and solid dispersions were analyzed by microTA. The thermal values obtained by microTA were compared with data obtained by more conventional techniques like differential scanning calorimetry. RESULTS: microTA was able to detect the drug in the waxy matrix. The technique was capable of showing that relatively large amorphous drug domains (up to 70 microm) are formed during the solidification of the solid dispersion. These amorphous domains are thermodynamically unstable and can crystallize upon aging. CONCLUSIONS: microTA was successfully applied to the physical characterization of solid dispersions. Local thermal analysis (LTA) offers a unique way to probe a selected area on the surface of the sample. It is capable of melting the drug locally without melting the lower melting point excipient. These results gave an understanding of the poor dissolution performance of these solid dispersions upon aging.