Purpose: Erectile dysfunction (ED) is the most important disorder after Premature ejaculation (PE) for sexual activity in Men. This study aims to formulate and clinically evaluate an oral disintegrating tablets (ODTs) containing Vardenafil Hydrochloride (VH) and Dapoxetine Hydrochloride (DH) for the concurrent treatment of ED and PE in men.
Methods: Compatibility between VH, DH and different excipients were checked using Differential Scanning Calorimetry (DSC) and Infra-red Spectroscopy (FTIR). VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Stability study was performed for the best chosen three formulae after 6 months’ storage at 40 ± 2 oC and 75 ± 5% RH. An in-vivo clinical comparative pharmacokinetic study was done one the most stable formula on healthy human subject in comparison to the commercial products containing DH (Levitra) and DH (Priligy).
Results: Results of DSC and FTIR revealed no interaction between VH, DH and different used excipients. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15 min. Stability study results showed that the formula D3 was the most stable one. In vivo study results from six healthy male volunteers showed shorter Tmax of VH from VH/DH ODT (formula D3) of 0.583 ± 0.129 hr and shorter Tmax of DH from VH/DH ODT (formula D3) of 0.625 ± 0.137 hr and showed AUC0–12 of VH from VH/DH ODT (formula D3) of 39.234 ± 10.932 ng/ml/hr and AUC0–12 of DH from VH/DH ODT (formula D3) of 531.681 ± 129.544 ng/ml/hr, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra) and (Priligy).
Conclusion: lyophilization technique is suitable for the preparation of ODTs of VH and VH/DH ODTs. Gelatin is a suitable matrix former for the preparation of ODTs that complies with suitable weight uniformity, friability, drug content uniformity, disintegration time, and release of VH from ODT. Addition of DH did not affect significantly the percent released of VH in SSF. The shorter Tmax of VH and DH obtained from the ODT formulation suggests a more rapid onset of action compared to the commercial products (Levitra) and (Priligy), respectively.
Mohamed El-Nabarawi– Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo
Khaled Elrefaie– Central Administration of Pharmaceutical Affairs (CAPA), Cairo, Egypt, Cairo, Al Qahirah