Enhanced Dissolution of Sildenafil Citrate Using Solid Dispersion with Hydrophilic Polymers: Physicochemical Characterization and In Vivo Sexual Behavior Studies in Male Rats.

Mohammed F Aldawsari,M Ali Aboudzadeh,Ameeduzzafar Zafar,Md Khalid Anwer,Gamal A Soliman,Mohammed Muqtader Ahmed,Saurabh Bhatia,Farhat Fatima

doi:10.3390/polym13203512

Abstract

Sildenafil citrate (SLC) is a frequently used medication (Viagra®) for the treatment of erectile dysfunction (ED). Due to its poor solubility, SLC suffers from a delayed onset of action and poor bioavailability. Hence, the aim of the proposed work was to prepare and evaluate solid dispersions (SDs) with hydrophilic polymers (Kolliphor® P188, Kollidon® 30, and Kollidon®-VA64), in order to enhance the dissolution and efficacy of SLC. The SLC-SDs were prepared using a solvent evaporation method (at the ratio drug/polymer, 1:1, w/w) and characterized by Differential Scanning Calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscope (SEM), drug content, yield, and in vitro release studies. Based on this evaluation, SDs (SLC-KVA64) were optimized, with a maximum release of drug (99.74%) after 2 h for all the developed formulas. The SDs (SLC-KVA64) were further tested for sexual behavior activity in male rats, and significant enhancements in copulatory efficiency (81.6%) and inter-copulatory efficiency (44.9%) were noted in comparison to the pure SLC drug, when exposed to the optimized SLC-KVA64 formulae. Therefore, SD using Kollidon®-VA64 could be regarded as a potential strategy for improving the solubility, in vitro dissolution, and therapeutic efficacy of SLC.

Highlights

Erectile dysfunction (ED) is the inability of a male to achieve and maintain erection for a sufficient period of time for satisfactory intercourse with a counterpart female partner [1]
solid dispersions (SDs) of Sildenafil citrate (SLC) were prepared by solvent evaporation method using three hyd4r.oCpohnilicclupsoiloynmsers as drug carriers, namely Kolliphor®poloxamer 188 (P188), Kollidon®30, and Kollidon®VA 64I.nTthheispsrteupdayre,dSDSDs sofsuScLcCeewdedreinpriempparoevdinbgy tshoelvdeinsstoelvuatipoonraratitoenanmdetsheoxudaul sbienhgatvhiroere inhymdaroleprhaitlsic
TphroevperdepthaereSdCSLDdsisusocclueetidoendcionmimpaprreodvitnogththeepduirsesodlurutigo.nTrhaeteoapntdimseizxeudal SD (SLC-KV64) system showed the maximum enhancement in dissolution rate compared to the pure SLC drug

Summary

Introduction

Erectile dysfunction (ED) is the inability of a male to achieve and maintain erection for a sufficient period of time for satisfactory intercourse with a counterpart female partner [1]. Millions of men around the world have some degree of ED, and more than twice that number are anticipated to be affected by 2025 [2,3]. SLC is an orally administered medication, selectively used to treat ED and pulmonary hypertension (PH). SLC absorbs quickly and acts within 1 h of oral administration, but due to a low aqueous solubility and hepatic first pass metabolism (~ 80% of administered dose), its relative bioavailability is 41% [4,5]. The solubility and bioavailability of SLC can improved by various means, such as, cyclodextrin complex [6,7], orodissovable films [8], dry foam tablets [9], salts and co-crystals [10], Selfnanoemulsifying drug delivery systems (SNEDDS) [11], and spray dried amorphous solid dispersions [12]. The advantages of SD have been mentioned in many investigations, including the improvement of dissolution rate and efficacy of poorly water insoluble drugs [13,14]

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Conclusion