Some Properties of Diazepam-Polyethylene Glycol 6000 Solid Dispersions and their Modification in the Presence of Stearic Acid of Polysorbate 80

Abstract

Physical mixtures and melts of diazepam and polyethylene glycol 6000 (PEG 6000) have been studied by Differential Scanning Calorimetry (DSC) and Differential Thermal Analysis (DTA). Problems were encountered in determining the precise position of the eutectic which contained <30% diazepam. Melts contained amorphous diazepam and, immediately after preparation, an unstable form of PEG 6000 which transformed on storage to a more stable form, probably folded crystals. Dissolution rates were determined by constant surface area methodology and were greatest in melts containing 15% diazepam. The inclusion of 1 or 5% polysorbate 80 or 1% stearic acid into the melts slightly increased the dissolution rates from dispersions containing 5, 10 or 15% diazepam but especially from dispersions containing 20% diazepam. A limited 4-week ageing study indicated that age-induced changes depended on both the storage temperature and diazepam concentration. The inclusion of either stearic acid or polysorbate 80 appeared not to protect dissolution rates against ageing