Transdermal delivery of tadalafil using a novel formulation

Abstract

The aim of this work was to investigate the transdermal gel loaded with tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5) in order to improve the solubility and bioavailability. The solubility of tadalafil in mixed solution of hydroxypropyl-b-cyclodextrin (HPCD), polyethylene glycol (PEG) 400 and tween 80 (T2 solution) was 260.8 ± 4.3 mg/mL and that of tadalafil in modified T2 (M-T2) solution, which tadalafil was dissolved in 20% (w/v) HPCD at first and then mixture solutions of PEG 400 and tween 80 were added, was increased to 344.9 ± 30.6 mg/mL. Four gel formulae were prepared, subsequently in vitro and in vivo skin permeation studies were carried out. Interestingly, tadalafil gel in M-T2 and oleic acid (OA) (F3) could promote the percutaneous absorption of tadalafil by 179.4% in vitro and increase AUC by 223% in vivo compared with tadalafil gel in the absence of M-T2 and OA (F1). Also, there was a finding that tadalafil gel in M-T2 and OA did not cause dermal irritations in an experimental animal.

Development of a Sildenafil Citrate Microemulsion-Loaded Hydrogel as a Potential System for Drug Delivery to the Penis and Its Cellular Metabolic Mechanism

“…where C d is the initial drug concentration in the donor compartment, and the slope is that of the cumulative amount of drug permeated versus the square root of time plot. The enhancement ratio (ER) was calculated by dividing the J ss of the optimised microemulsion system by that of the sildenafil suspension [4,19,20].…”

“…It is available only in the form of tablets. Some studies have shown that sildenafil citrate or PDE inhibitor drugs can be administered topically [4][5][6][7]. The transdermal delivery of sildenafil citrate through a local tissue area could be considered as an alternative to the oral route, in order to avoid adverse effects, shorten the onset time, and sustain the therapeutic effects for longer periods [1].…”

“…These cells hinder the penetration of drugs. This skin barrier is overcome by using the most widely implemented approach involving chemical penetration enhancers that can, ideally, safely and reversibly alter the physicochemical nature of the stratum corneum to facilitate drug delivery through the skin [4].…”

Gellan Gum-Based Hydrogel for the Transdermal Delivery of Nebivolol: Optimization and Evaluation

“…It is a clear, viscous, nonvolatile, nonirritating, low-molecular-weight polyether compound composed of polyethylene and water. It is widely used as a solvent and permeation enhancer in transdermal formulations [25]. Tween 80, a nonionic surfactant, is a solubilizing agent for a variety of substances and is included in the formulation to enhance the solubility of nebivolol.…”

Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents

“…Topical and transdermal drug delivery can offer great potential for non-invasive and non-oral administration of poorly bioavailable therapeutic agents (Kalia et al., 2004 ; Chen et al., 2016 ; Jacobs et al., 2016 ; Zidan et al., 2016 ). Drug delivery through the skin has merits in improving patient compliance and avoiding gastrointestinal irritation and hepatic first-pass effect (Baek & Cho, 2016 ; Jain et al., 2017 ). Moreover, topical delivery can enhance the efficiency of drug targeting to the skin and adjacent tissues, while transdermal delivery can provide a constant systemic exposure profile, potentially reducing several side effects caused by fluctuating blood drug concentrations (Jung et al., 2015 ; Patel et al., 2016 ; Rao et al., 2016 ).…”