Study On In Vitro Dissolution And Establishment Of The Dissolution Methods Of Poorly Souble Drugs

Dissolution is the performance parameter that indicating the rate and degree of pharmaceutical ingredient in solid dosage forms (tablets and capsules et al) dissolving in medium under specified condition. Now dissolution test has been widely applied as evaluating and screening tool of formulations and preparation process, quality evaluation of solid preparation, predicting bioavailability on the basis of dissolution result as well as in-vivo and in-vitro correlation, it follows that dissolution testing has already been one of most important projects in drug quality control system. However, it is controversial that whether methods of dissolution in current standards could be used as an approach to reflect bioavailability, especially for poorly water-soluble drug. For example, in order to making drug dissolving out completely, some conditions setting in dissolution test are so vigorous that don’t conform with actual physiological environment of gastrointestinal tract, which may result in differing in clinical efficacy of the same kind of medicine from varied manufacturers. Therefore, it is important and necessary to explore in establishing dissolution methods which could reflect both inner quality and bioavailability of drugs, for better controlling drug quality strictly and ensuring the effectiveness and safety of drugs in clinical application.In this paper, according to study the solubility and apparent oil-water partition coefficient of telmisartan, carbamazepine and carvedilol, the dissolution parameters including medium, volume and rotate speed, etc. had been improved, which were with high similarity to physiological environment of gastrointestinal tract. Besides, the dissolution behaviors of medicines provided by different manufacturers had been studied and compared with dissolution profiles in Orange Book. Experimental results showed that optimized methods of dissolution had preferable discrimination, and could evaluate the quality of drugs more objectively, moreover, the update dissolution condition could better simulate physiological environment, which had satisfied in vivo-in vitro correlation. In addition, this paper carried out Raman mappings determination of different samples by Laser confocal micro Raman spectrometer, the results showed that carbamazepine tablets and carvedilol tablets produced by varied manufacturers had no relationship between differences of dissolution behavior and crystal forms, telmisartan tablets emerged three kinds of Raman spectrum, and corresponding dissolution behavior was different because of diverse formulations and preparation process.This research focused on dissolution test of poorly water-soluble drugs which had distinctive physicochemical properties, studied dissolution curves of drugs with different formulation and preparation process as per optimized conditions. It could provide suggestions and guidance for researching and establishing rational dissolution methods,also would be an reference for further study of in vivo-in vitro correlation of drugs.