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

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.

Sildenafil Citrate adjuvant Ovulation Induction Therapy with Clomiphen Citrate in Polycystic Ovarian Syndrome for Successful Ovulation; Cross-Over, Randomized Controlled Trial

Background Sildenafil Citrate (Respatio® 20 mg) as an adjuvant therapy in induction of ovulation along with Clomiphen Citrate (Clomid ®), is settled to enhance the endometrial receptivity through enhancing endometrial thickness and echogenicity. Yet, the exact role of Sildenafil in ovulation itself is still under study assuming that through increasing ovarian blood flow as a part of pelvic blood flow, will enhance the ovulation measured by the number and diameter of the growing follicles. Aim of the Work The aim of this study is to evaluate the efficacy of sildenafil citrate on the ovulation in PCOS women undergoing induction of ovulation using clomiphene citrate. Patients and Methods The current study was conducted in Ain Shams University Maternity Hospital- Infertility outpatient clinic during the period between January 2018 and December 2019. It included a total number of 595 patients who either were assessed for eligibility of the study, of which, 141 were excluded due to non-matching inclusion criteria or had exclusion criteria. 22 patients did not consent to participate in the study432 patients were matched, randomized and allocated to the two groups of the study each with 216 and received induction of ovulation according to the protocol of the study with either Clomiphen Citrate and Sildenafil Citrate or Clomiphen Citrate only, then they were followed up for 3 months. Those who didn't get pregnant given 2 months with no induction to wash over the effect and croos over the groups was done and followed up for another 3 months. Results Pregnancy test was positive in 39.8% in Clomiphen/Sildenafil group compared to just 30.1% in Clomiphen group. The patients that did not have positive pregnancy test in the first three months, have a rest for 2 months and then cross over of the groups took place. 145 patients shifted to Clomiphen/ Sildenafil protocol while 126 patients shifted to Clomiphen protocol and follow up for 3 months again and positive pregnancy test was 38% and 25% in the two groups in order. Conclusion using sildenafil citrate in patients with PCO syndrome undergoing induction of ovulation increases the chemical and clinical pregnancy rates through not only increasing the endometrial thickness and improving the endometrial pattern with improving the endometrial Doppler indices but also improving the ovulation by improving the ovarian arteries Doppler indices as well.