Papaverine hydrochloride containing nanostructured lyotropic liquid crystal formulation as a potential drug delivery system for the treatment of erectile dysfunction

Abstract

PurposePapaverine hydrochloride (PaHCl) is an old, well-known drug with spasmolytic activity but it has therapeutic effect in erectile dysfunction, too. As an intracavernous injection, it is not used in urologic clinics today because the side effects of the injection are pain, scarring or priapism. Our aim was to develop and test a topical semi-solid preparation containing PaHCl that would provide an alternative administration option by eliminating the undesirable side effects of the injection.Materials and methodsLyotropic liquid crystal (LLC) systems were formulated as a semi-solid preparation with different concentrations of PaHCl. The characterization of the LLC structure was performed by polarization microscopy using a Leica image analyzer and rheological measurements. The drug diffusion and penetration tests were performed with in vitro synthetic membrane and an ex vivo human epidermis, using Franz diffusion cell to test the skin penetration of PaHCl. Human skin was investigated by Raman microscope to visualize the Active Pharmaceutical Ingredient (API) in different skin layers.ResultsThe results of diffusion and penetration showed reverse concentration dependency. The in vitro and ex vivo studies correlated with each other and the results of Raman microscopy. The LLC structure influenced the penetration results, the lower viscosity and lamellar structure increased penetration through the skin.ConclusionBased on our results, a PaHCl containing topically used LLC formulation may be a suitable and effective alternative to the injectable formulation.

Novel In Vitro Investigational Methods for Modeling Skin Permeation: Skin PAMPA, Raman Mapping

“…32 scans were registered for each spectrum, with an exposure time of 6 s. The optics magnitude in the Raman microscope was 10 with a 25 μm slit aperture. Data acquisition and analysis were accomplished using OMNICTM8.2 for Dispersive Raman software package (ThermoFisher Scientific Inc., Waltham, MA, USA) [ 24 , 27 ].…”

“…Raman spectroscopy can give information about the spatial distribution of the drug in the skin layers based on the characteristic vibrational energy levels of the structure of a molecule. This semi-quantitative technique is suitable for monitoring the permeation of exogenous materials into the skin layers [24][25][26][27][28].…”

Methods to Evaluate Skin Penetration In Vitro

“…Therefore, this method is promising for discovering modifications in the structure of skin components. In addition, it is good for following up the penetration/permeation of APIs [114,115]. Nowadays, Raman microscopy is a powerful technique to properly understand skin structure and percutaneous drug delivery [111,[116][117][118].…”

A Review of Current and Emerging Therapeutic Options for Erectile Dysfunction

“…The transdermal bioavailability of a vardenafil nanoethosome film was reported to be two-fold higher than the oral bioavailability from an aqueous suspension [40]. Papaverine with lyotropic liquid crystals has been shown to provide an effective alternative to injectable formulations both in vitro and ex vivo [41].…”