Department of Pharmaceutics, Khalsa College of Pharmacy, Amritsar, Punjab, 143001, India.
Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, Punjab, 143001, India.
AAPS PharmSciTech. 2022 Jul 28;23(6):209. doi: 10.1208/s12249-022-02367-w.
The present study is focused on the use of solid dispersion technology to triumph over the solubility-related problems of bexarotene which is currently used for treating various types of cancer and has shown potential inhibitory action on COVID-19 main protease and human ACE2 receptors. It is based on comparison of green locust bean gum and synthetic poloxamer as polymers using extensive mechanistic methods to explore the mechanism behind solubility enhancement and to find suitable concentration of drug to polymer ratio to prepare porous 3 generation solid dispersion. The prepared solid dispersions were characterized using different studies like X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), differential scanning calorimetry (DSC), and particle size analysis in order to determine the exact changes occurred in the product which are responsible for enhancing solubility profiles of an insoluble drug. The results showed different profiles for particle size, solubility, dissolution rate, porosity, BET, and Langmuir specific surface area of prepared solid dispersions by using different polymers. In addition to the comparison of polymers, the BET analysis deeply explored the changes occurred in all dispersions when the concentration of polymer was increased. The optimized solid dispersion prepared with MLBG using lyophilization technique showed reduced particle size of 745.7±4.4 nm, utmost solubility of 63.97%, pore size of 211.597 Å, BET and Langmuir specific surface area of 5.6413 m/g and 8.2757 m/g, respectively.
本研究聚焦于使用固体分散体技术克服贝沙罗汀(目前用于治疗各种癌症,且显示出对 COVID-19 主蛋白酶和人 ACE2 受体有潜在抑制作用)的溶解度相关问题。本研究基于比较天然野绿豆胶和合成泊洛沙姆作为聚合物,使用广泛的机制方法来探索溶解度增强背后的机制,并找到合适的药物与聚合物比例浓度来制备第三代多孔固体分散体。通过不同的研究,如 X 射线衍射(XRD)、热重分析(TGA)、扫描电子显微镜(SEM)、BET、差示扫描量热法(DSC)和粒度分析,对制备的固体分散体进行了表征,以确定产品中发生的具体变化,这些变化是提高难溶性药物溶解度的原因。结果表明,使用不同的聚合物,制备的固体分散体的粒径、溶解度、溶出速率、孔隙率、BET 和 Langmuir 比表面积呈现出不同的分布。除了聚合物的比较之外,BET 分析还深入探讨了当聚合物浓度增加时所有分散体中发生的变化。使用冷冻干燥技术制备的 MLBG 优化固体分散体显示出减小的粒径为 745.7±4.4nm,最大溶解度为 63.97%,孔径为 211.597Å,BET 和 Langmuir 比表面积分别为 5.6413m/g 和 8.2757m/g。