Solubility-Permeability Interplay of Hydrotropic Solubilization Using Response Surface Methodology

Background: The solubility/dissolution of a drug in the gastrointestinal (GI) region and the permeability of a drug through the GI membrane are the two key parameters governing drug absorption. Poor aqueous solubility is the rate-limiting factor for the absorption of poorly soluble drugs through the GI region. Objective: The purpose of this work is to investigate the influence of two different hydrotropes, namely sodium benzoate (SB), and nicotinamide (NA), at different levels (10-40%) and in combination on the solubility and permeability of poorly soluble drug glibenclamide (GLB). The work will find out, whether the solubility enhancement of glibenclamide using hydrotropes and hydrotropic blends also affects the GI permeability of glibenclamide. Methods: A 32 full factorial design was employed to study the influence of hydrotropic blends of sodium benzoate and nicotinamide on the solubility and permeability of GLB. The solubility and permeability of drugs at different levels (10-40%) of hydrotropes (SB, NA) and their blends are determined using a magnetic stirrer and in vitro Franz diffusion cell, respectively. Results: The results of preliminary studies revealed an increase in the solubility and reduction in the apparent permeability of GLB as a function of increasing levels of both hydrotropes. Conclusion: In this work, it was found that an increase in solubility with hydrotropes results in a decrease in permeability of GLB. The solubility enhancement and the permeability decrease were observed more in hydrotropic blends in comparison to individual hydrotropes. Therefore, it is concluded that both factors, solubility and permeability, must be optimized to achieve appreciable gains in bioavailability.