目的:盐酸雷洛昔芬(RLX)被广泛用于治疗骨质疏松症,在显著的首过代谢后,RLX的生物利用度仅保留2%。除了来自BCS二级,RLX不溶于水。因此,当前研究的目标是通过使用β环糊精(β-CD)作为载体和泊洛沙姆407的固体分散体创建包合物来改善RLX溶解度。
方法:包合物和固体分散体使用多种技术制备,包括揉捏,共沉淀,以及使用不同药物与载体比率(1:1、1:2和1:3)的物理混合和固体分散体。
结果:与普通RLX相比,使用共沉淀法制备的包合物的水溶性提高了9倍。为了评估优化后的复杂的兼容性,热分析,和结晶度,X射线衍射,差示扫描量热法,和傅里叶变换红外光谱。XRD和DSC研究结果表明RLX由结晶态转变为非晶态。基于结果,IC-6表现出有效的水溶性。然而,通过两种技术的比较,与固体分散体相比,β-CD络合方法显示出药物溶解度的显着提高。
OBJECTIVE: Raloxifene hydrochloride (RLX) is used extensively in the treatment of osteoporosis, only 2% of RLX\'s bioavailability remains after a significant first pass metabolism. Besides coming from BCS class II, RLX is not very soluble in water. Thus, the goal of the current study was to improve RLX solubility by creating an inclusion complex using β cyclodextrin (β-CD) as a carrier and solid dispersion with Poloxamer 407.
METHODS: Inclusion complex and solid dispersion were made using a variety of techniques, including kneading, co-precipitation, and physical mixing and solid dispersion using different drug to carrier ratios (1:1, 1:2 and 1:3).
RESULTS: Inclusion complex made using the co-precipitation method had shown 9-fold improvements in water solubility when compared with plain RLX. In order to assess the optimized complex\'s compatibility, thermal analysis, and crystallinity, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy were used. The XRD and DSC study\'s results indicated that RLX changed from a crystalline to an amorphous state. IC-6 exhibits effective water solubility based on the outcome. However, upon comparison of the two techniques, the β-CD complexation method shown an impressive rise in drug solubility when compared to solid dispersion.