Zaghian Mahsa, Homayouni Alireza, Keshavarz Zahra, Dayani Ladan, Fakhari Zeinab, Osooli Fatemeh Sadat
Pharmacy Students' Research Committee, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Research and Development Department, Goldaru Pharmaceutical Company, Isfahan, Iran.
Res Pharm Sci. 2025 Aug 25;20(4):566-579. doi: 10.4103/RPS.RPS_105_23. eCollection 2025 Aug.
Valsartan (Val), administered for hypertension, exhibits poor water solubility, resulting in low oral bioavailability. This study aimed to enhance the dissolution of Val by preparing orodispersible tablets (ODT) using solid dispersion (SD) technology with PVP and HPMC as hydrophilic carriers.
After preparation of the SDs and physical mixtures of Val: PVP and Val: HPMC at various ratios, the physicochemical characteristics of these mixtures were analyzed. Then, the ODTs were prepared using the best SD sample and evaluated through USP tests.
FINDINGS/RESULTS: The saturation solubility of Val: PVP 1:1 and 1:2 at pH 6.8 was notably higher than that of pure Val. The SDs exhibited a superior dissolution rate compared to pure Val and its physical mixtures. Increasing the drug/carrier ratio resulted in a decrease in the percentage of drug in SD, with Val: PVP 1:1 SD showing significantly higher drug loading percentage compared to other formulations. All formulations exhibited entrapment efficiencies above 80%. Also, the flow of the SDs was good based on the Hausner ratio.
The SDs exhibited more favorable attributes compared to pure Val and its physical mixtures. The research suggests that PVP and HPMC are effective carriers for improving the solubility and dissolution rate of Val. Additionally, mannitol was identified as a beneficial excipient for achieving the desired properties of ODTs. The findings can be applied to other drugs with similar solubility issues, paving the way to improve therapeutic outcomes for patients.
用于治疗高血压的缬沙坦（Val）水溶性差，导致口服生物利用度低。本研究旨在通过使用聚维酮（PVP）和羟丙甲纤维素（HPMC）作为亲水性载体的固体分散体（SD）技术制备口腔崩解片（ODT）来提高缬沙坦的溶出度。
以不同比例制备缬沙坦与PVP、缬沙坦与HPMC的固体分散体及物理混合物后，分析这些混合物的理化特性。然后，使用最佳的固体分散体样品制备口腔崩解片，并通过美国药典测试进行评估。
缬沙坦与PVP 1:1和1:2在pH 6.8时的饱和溶解度显著高于纯缬沙坦。与纯缬沙坦及其物理混合物相比，固体分散体表现出更高的溶出速率。增加药物/载体比例导致固体分散体中药物百分比降低，缬沙坦与PVP 1:1固体分散体的载药百分比显著高于其他制剂。所有制剂的包封率均高于80%。此外，基于豪斯纳比，固体分散体的流动性良好。
与纯缬沙坦及其物理混合物相比，固体分散体表现出更有利的特性。研究表明，PVP和HPMC是提高缬沙坦溶解度和溶出速率的有效载体。此外，甘露醇被确定为实现口腔崩解片所需特性的有益辅料。这些发现可应用于其他具有类似溶解度问题的药物，为改善患者治疗效果铺平道路。
