An effective approach for the management of men’s sexual dysfunction via local administration of Sildenafil/cyclodextrin-loaded hydrogels

Objectives This study aimed to enhance the bioavailability of Sildenafil via cyclodextrin inclusion complexation and to formulate various hydrogel systems containing modified Sildenafil as an alternative, safe treatment for erectile dysfunction.Significance Oral administration of Sildenafil is accompanied by severe hypotension, making this drug contraindicated for patients with cardiac dysfunction, which may lead to fatal acute and severe hypotension. Therefore, topical and local administration is considered an option to avoid side effects accompanying oral administration.Methods The current work was divided into three distinct segments. First, we enhanced the solubility of sildenafil by forming and characterizing inclusion complexes with hydroxypropyl-β-CD. Secondly, hydrogels were prepared and characterized using different gelling agents, including Carbopol 940, HPMC, and Gelatin. Lastly, the selected hydrogel system was utilized for the in vivo application in participants (n = 60). The gel formulation was applied locally on the penis 0.5 h before intercourse, and both intravaginal latency time (IVLT) and International Index of Erectile Function (IIEF-5) were monitored before and after drug application. Besides, irritation studies were conducted on rat models.Results The drug solubility and dissolution rate were markedly improved via inclusion complexation with cyclodextrin. Also, the medicated hydrogel formulations exhibited good consistency, spreadability, and homogeneity. Notably, the gel composed of HPMC, loaded with modified Sildenafil, demonstrated the fastest release rate compared to the other gelling agents. The in vivo results revealed a remarkable improvement in both erectile dysfunction and premature ejaculation parameters (IVLT and IIEF-5). Also, the results showed that there is no sign of irritation upon application.Conclusion The modified Sildenafil hydrogel is an alternative and safe therapy for patients suffering from erectile dysfunction and premature ejaculation since this route of administration avoids severe risks accompanying oral administration.