Osman Shaaban K, Yassin Abobakr M, Yassin Taher M, Mohammed Ahmed M, Abdelsalam Ahmed M, Mahdi Wael A, Alshehri Sultan, El Hamd Mohamed A, Abdellatif Ahmed A H, Amin Mohammed A, Taha Emad A
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.
Department of Pharmacy Investigator, Pharmacy Department, Sohag, Egypt.
AAPS PharmSciTech. 2025 Jan 16;26(1):37. doi: 10.1208/s12249-024-03027-x.
The present work focuses on the production of sildenafil co-evaporates loaded emulgels as topical dosage forms for the treatment of premature ejaculation and erectile dysfunction. Topical administration of sildenafil citrate (SILD) co-evaporates is expected to improve the bioavailability profile of the drug and to avoid the severe side effects accompanying the traditional SILD dosage forms, especially for prohibited cardiovascular cases. Firstly, the solubility of SILD was improved via solid dispersion via co-evaporation technique using PEG-5KDa and PVP-K90 as hydrophilic carriers. The modified co-evaporates were characterized by DSC, XRD, and solubility studies. Different emulgels, loaded with SILD co-evaporates, were formulated and characterized by different analyses including the viscosity, stability, spreadability, and in vitro release studies. Finally, the clinical activity of the chosen formula was accomplished via the application of the emulgels on volunteers suffering from erectile dysfunction. The results showed that the prepared SILD/PVP K90 of 1:2 w/w ratio exhibited the highest solubility and dissolution rate. All formulated emulgels exhibited good physicochemical properties. Especially, the emulgel formula composed of 2%w/v HPMC, loaded with SILD /PVP- K90, revealed the highest release rate. The release mechanism of SILD from emulgels fits with the Korsmeyer Peppas mechanism. The results of in vivo studies indicated a significant improvement of both IVLT and IIEF-5 parameters in mild to moderate ED, accompanied by PE. The modified SILD emulgel is an alternative promising and safe transdermal drug delivery system for the management and treatment of mild to moderate ED with PE.
本研究聚焦于制备西地那非共蒸发物负载的乳胶凝胶，作为治疗早泄和勃起功能障碍的局部剂型。预计局部施用枸橼酸西地那非（SILD）共蒸发物可改善药物的生物利用度，并避免传统SILD剂型伴随的严重副作用，特别是对于禁忌的心血管病例。首先，通过使用聚乙二醇-5 kDa和聚乙烯吡咯烷酮-K90作为亲水性载体的共蒸发技术，通过固体分散提高了SILD的溶解度。通过差示扫描量热法（DSC）、X射线衍射（XRD）和溶解度研究对改性共蒸发物进行了表征。制备了不同的负载SILD共蒸发物的乳胶凝胶，并通过包括粘度、稳定性、铺展性和体外释放研究在内的不同分析进行了表征。最后，通过将乳胶凝胶应用于患有勃起功能障碍的志愿者来完成所选配方的临床活性。结果表明，制备的重量比为1:2的SILD/聚乙烯吡咯烷酮-K90具有最高的溶解度和溶解速率。所有制备的乳胶凝胶均表现出良好的物理化学性质。特别是，由2%w/v羟丙基甲基纤维素（HPMC）组成、负载SILD/聚乙烯吡咯烷酮-K90的乳胶凝胶配方显示出最高的释放速率。SILD从乳胶凝胶中的释放机制符合Korsmeyer Peppas机制。体内研究结果表明，在伴有早泄的轻度至中度勃起功能障碍患者中，国际勃起功能指数（IIEF）-5和阴道内射精潜伏期（IVLT）参数均有显著改善。改性SILD乳胶凝胶是一种有前景且安全的经皮给药系统，可用于管理和治疗伴有早泄的轻度至中度勃起功能障碍。
