Influence of lipophilia and of the vehicle used in the transdermal absorption of novel benzimidazole compounds with possible anti-HIV activity.
The molecules 2-pyridin-3-yl-1H-benzimidazole and 2-pyridin-3-yl-1-(3,4,5-trimethoxybenzoyl)-1H-benzimidazole are compounds that have been synthesized with the aim of finding new inhibitors of the reverse transcriptase enzyme, which is key in the process of cellular contagion of HIV. Because of the possible biological activity of these molecules, it is important to determine if some factors exist that condition their absorption across membranes. In this article, we studied the transdermal absorption of both molecules when included in solutions and microemulsions; the latter of these systems is known for their capacity to promote absorption. On the basis of the results obtained, it was determined that the absorption of 2-pyridin-3-yl-1H-benzimidazole is better in solutions than in microemulsions. This is attributed to the system of microemulsions used (myristic isopropyl ester/water/Tween 80: Span 80: 1.2 Octanediol 3:1:1.2 v/v/v), which does not provide an adequate thermodynamic activity for this molecule. In contrast, the absorption of 2-pyridin-3-yl-1-(3,4,5-trimethoxybenzoyl)-1H-benzimidazole is independent of the vehicle in which it is in, a fact attributable to the limitation of absorption due to parameters proper to this molecule, such as the value of its Log Poct, its molecular weight, or its low solubility in water. In addition, it was possible to implement a methodology based on HPLC to determine the Log P of these compounds. In this way, it was determined that the inclusion of 3,4,5-trimethoxybenzoyl moiety to the molecule 2-pyridin-3-yl-1H-benzimidazole, despite increasing the Log Poct value of this molecule up to a value considered optimal for absorption through membranes, did not produce an increase in transdermal absorption. In fact, its molar absorption diminished by more than 50%, which is attributable to the increase of molecular weight and the decrease of affinity for water that the inclusion of this group causes.
Alvarez-Figueroa
María Javiera
MJ
Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile. mjalvare@uc.cl
Pessoa-Mahana
Carlos David
CD
González-Bustamante
Daniela Andrea
DA
D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D004655:Emulsions; D008970:Molecular Weight; D014677:Pharmaceutical Vehicles; D012869:Skin Absorption; D012995:Solubility; D013329:Structure-Activity Relationship; D013552:Swine
D019380:Anti-HIV Agents; D001562:Benzimidazoles; D004655:Emulsions; D014677:Pharmaceutical Vehicles