Abstract

AQUEOUS SOLUBILITY OF NEVIRAPINE: ENHANCEMENT BY COSOLVENCY AND MICELLIZATION

*Gerald W. Ugodi, Ndidiamaka N. Okorie, Adora Agatha Ugwu and Chika J. Mbah

Abstract

Cosolvency and micellar solubilization are powerful techniques for dissolving hydrophobic compounds in aqueous solutions. Drugs with poor aqueous solubility problems often times exhibit low bioavailability as a result poor dissolution rate. This variability in bioavailability of orally administered drugs has necessitated the classification of drugs based on the correlation between their physicochemical properties (namely aqueous drug solubility and drug permeability) and in vivo biological activities (Biopharmaceutics Classification System). The objective of this study was to investigate the effect of some solubilizing agents on the aqueous solubility of nevirapine. Solubility of nevirapine was determined in aqueous mixture of cosolvents (glycerol, propylene glycol, polyethylene glycol 400) and surfactants (tween 20, tween 80, sodium lauryl sulfate, cetrimide). Excess of nevirapine was introduced directly into each of the mixed solvent at room temperature 25 ±1oC. Equilibrium method (shake-flask technique) was employed. After equilibrium, the solutions were filtered and analyzed spectrophotometrically. The results show logarithm linear relationships between nevirapine solubility in water-cosolvent mixtures and cosolvent fraction volume. The solubilization power (σ) or the slope is used to describe the drug-cosolvent-water system. In all cases, the least polar cosolvent, polyethylene glycol 400 gave the highest σ value and the most polar cosolvent, glycerol gave the lowest σ value. With the surfactants, linear relationships between the solubility of nevirapine in water-surfactant mixtures and surfactant concentration were observed. The slopes of these plots or solubilization capacities, k were higher for ionic and nonionic surfactants than for cationic surfactant. Micellar partition coefficients of nevirapine are linearly related to the free energy of solubilization. The result of the study shows that aqueous solubility of nevirapine is significantly improved by cosolvency and micellization. Significance of the solubility data in relation to the development of formulations has also been discussed in this study.

Keywords: Nevirapine, aqueous solubility, cosolvency, micellization.