PREFORMULATION STUDIES ON SOLID DISPERSIONS CONTAINING TRIAMTERENE OR TEMAZEPAM IN POLYETHYLENE GLYCOLS OR GELUCIRE 44 14 FOR LIQUID FILLING OF HARD GELATIN CAPSULES

Solid dispersions of triamterene or temazepam in polyethylene glycols or gelucire 44/14 have been investigated. The phase equilibria of the drugs and carriers were determined by Differential Thermal Analysis and Hot Stage Microscopy. Particle Size Analysis was carried out using double image microscopy, whilst phase solubility techniques and dissolution methods were used to study solubility, dissolution and ageing. It has been shown that triamterene forms monotectics with polyethylene glycols and gelucire 44/14 and temzepam shows partial solubility. The effect of the carriers on particle size depends on the solubility of the drug in the carrier and size reduction is observed where the drug is soluble in the carrier. The aqueous solubilities of both drugs are increased by PEGs and gelucire 44/14 with the latter producing greater increases. The carriers, PEG 1000, PEG 1500 and gelucire 44/14 also increased dissolution rates of both drugs giving three- to four-fold increases compared with the higher molecular weight PEGs. Ageing effects observed for temazepam-PEG solid dispersions were found to be reduced by the use of lower molecular weight PEGs or gelucire 44/14.