Khan Waqas Haider, Asghar Sajid, Khan Ikram Ullah, Irfan Muhammad, Alshammari Abdulrahman, Riaz Rajoka Muhammad Shahid, Munir Rabia, Shah Pervaiz A, Khalid Ikrima, Razzaq Fizza Abdul, Khalid Syed Haroon
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh, 11451, Saudi Arabia.
Heliyon. 2023 Sep 1;9(9):e19658. doi: 10.1016/j.heliyon.2023.e19658. eCollection 2023 Sep.
BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.
BCS II类药物表现出低水溶性和高渗透性。这类药物通常具有不完全或不稳定的吸收特征。本研究旨在预测β-环糊精（βCD）和不同亲水性聚合物（泊洛沙姆188（PXM - 188）、聚乙烯吡咯烷酮（PVP）和尤特奇（SOLO））对疏水性模型药物利伐沙班（RIV）饱和溶解度和溶出曲线的影响。通过捏合和溶剂蒸发法制备了药物与环糊精重量摩尔比为1:1、1:2和1:4的βCD二元包合物。用βCD评估疏水性模型部分的饱和溶解度，以探究饱和溶解度的增加情况。进行溶出试验以评估所制备的二元包合物在水性介质中的药物释放。使用傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、X射线衍射（XRD）和扫描电子显微镜（SEM）技术进行固态分析。与纯药物相比，二元复合物（药物：βCD摩尔比为1:2 w/w）在溶解度增强和药物释放方面表现出最佳性能。此外，用亲水性聚合物SOLO、PVP K - 30和PXM - 188以0.5%、1%、2.5%、5%和10%的比例制备三元包合物，以优化通过捏合（KN）和溶剂蒸发（S.E）法制备的二元制剂RIV:βCD（1:2）。研究结果表明，在三元制剂中（1:2药物：βCD：10% SOLO S.E）饱和溶解度和溶出速率提高最为显著。FTIR、DSC、XRD和SEM分析也支持了三元包合作用提高模型药物溶解度和改善溶出曲线的结果。因此，可以得出结论，与二元组合相比，三元包合体系在提高疏水性模型药物利伐沙班的溶解度和溶出度方面更有效。
