The Relationship between Solubility and Transdermal Absorption of Tadalafil.

Mehdi Khoshbakht,Hamed Hamishehkar,Abolghasem Jouyban,Saeed Ghanbarzadeh

doi:10.15171/apb.2015.056

Mehdi Khoshbakht, Hamed Hamishehkar + Show 2 more

Open Access

https://doi.org/10.15171/apb.2015.056

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Abstract

The aim of this study was to find a relationship between drug solubility and its transdermal permeation and find the best vehicle composition to improve transdermal permeation of Tadalafil. Pure or binary mixtures of commonly used solvents in pharmaceutical sciences including ethanol, glycerin, N-methyl pyrrolidone (NMP), polyethylene glycol (PEG) 400 and propylene glycol (PG) were evaluated for drug solubility and transdermal delivery through the exercised rat skin employing Franz diffusion cells. Tadalafil showed higher solubility in NMP compared to the other solvents. The amount of Tadalafil permeation from the pure vehicles was ranked as follow: Ethanol >glycerin >NMP>PEG 400 >PG. Furthermore, the solubility and transdermal delivery from binary mixtures of NMP and PG were higher than that obtained from pure PG, and accordingly, both increased with increasing NMP concentration in the binary solvent mixtures. The Flux values were determined as following order for Ethanol>NMP>glycerin>PG>PEG 400. Generally, increase in Tadalafil solubility resulted in a decrease in its skin penetration rate and amount. However, NMP exhibited substantial drug skin penetration rate and amount accompanying with appropriate drug solvency. In conclusion, the results of this study introduced NMP as a solvent suitable for application in the formulation of topically applied drug delivery systems.

Highlights

Transdermal and dermal delivery systems represent an attractive alternative route of administration to oral delivery systems, which are available for systemic and local effect of drugs
Results indicated that the solubility of Tadalafil was increased significantly via increasing the ratio of N-methyl pyrrolidone (NMP) in the binary solvent mixtures with propylene glycol (PG)
The studied solvents are routinely used in the formulation of TDDSs, few disadvantages are reported such as skin dryness using ethanol[35] as well as sticky and greasy characteristics for glycerin[36] which cause patient incompliance and even stop the treatment procedure

Summary

Introduction

Transdermal and dermal delivery systems represent an attractive alternative route of administration to oral delivery systems, which are available for systemic and local effect of drugs. Various strategies have been employed in attempts to improve the efficacy of topical delivery of drugs, including iontophoresis, electroporation, occlusion and ultrasound.[5,6,7,8,9] an alternative approach is to use chemicals, known as permeation enhancers, which are materials that can partition into, and interact with, skin constituents to induce a temporary and reversible decrease in the skin barrier properties.[10,11] The therapeutic effects of transdermal formulations depend on the drug action and on other structural factors of the vehicle.

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