Murtaza Ghulam
Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
Acta Pol Pharm. 2012 Jul-Aug;69(4):581-90.
Fairly soluble drugs in gastrointestinal (GI) media exhibit complete oral absorption, and thus good bioavailability. About 40% of drugs are not soluble in water in practice and therefore are slowly absorbed, which results in insufficient and uneven bioavailability and GI toxicity. Thus, most exigent phase of drug development practice particularly for oral dosage forms is the enhancement of drug solubility and thereby its oral bioavailability. Solubility, an important factor to achieve desired plasma level of drug for pharmacological response, is the phenomenon of dissolution of solid in liquid phase resulting in a homogenous system. This review describes various traditional and novel methodologies proposed for solubility enhancement of simvastatin, and ultimately improvement in its bioavailability. For simvastatin, solubility is a crucial rate limiting factor to achieve its desired level in systemic circulation for pharmacological response. Thus, problematic solubility of simvastatin is a main challenge for dosage form developing researchers. Various procedures, illustrated in this review, have been successfully employed to improve the simvastatin solubility for its bioavailability enhancement; however, successful improvement essentially depends on the assortment of technique. Among all the solubility enhancement techniques, solid dispersion method, in terms of ease and efficiency is most promising and routinely employed technique to resolve the solubility problems of simvastatin.
在胃肠道（GI）介质中溶解度适中的药物呈现出完全的口服吸收，因此具有良好的生物利用度。实际上，约40%的药物不溶于水，因此吸收缓慢，这导致生物利用度不足且不均匀，以及胃肠道毒性。因此，药物研发实践中，尤其是口服剂型最迫切的阶段是提高药物溶解度，进而提高其口服生物利用度。溶解度是实现药物达到药理学反应所需血浆水平的一个重要因素，它是固体在液相中溶解形成均匀体系的现象。本综述描述了为提高辛伐他汀溶解度并最终改善其生物利用度而提出的各种传统和新型方法。对于辛伐他汀来说，溶解度是在体循环中达到药理学反应所需水平的关键限速因素。因此，辛伐他汀存在的溶解度问题是剂型研发研究人员面临的主要挑战。本综述中阐述的各种方法已成功用于提高辛伐他汀的溶解度以增强其生物利用度；然而，成功的改善在本质上取决于技术的选择。在所有提高溶解度的技术中，就简便性和效率而言，固体分散法是解决辛伐他汀溶解度问题最有前景且常规使用的技术。
