Abstract

Etravirine, an antiretroviral agent, used in the treatment of human immunodeficiency virus belongs to biopharmaceutical classification system classification IV. The reported solubility of the drug is 0.0169 mg/ ml. In the present study, an attempt was made to enhance the solubility of etravirine by crystal engineering technique. The cocrystallization method was carried out using 12 different coformers and each coformer was studied in two different stoichiometric ratios. A preliminary screening of all the cocrystals was done by determination of melting point and solubility. A statistical evaluation of all the cocrystals on solubility was carried out at a significance level of p<0.05. The best cocrystals were subjected to drug content, in vitro drug release, solid-state study (fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction) and stability study for 3 mo. Coformer benzoic acid showed a significant improvement in etravirine solubility in the drug:coformer ratio of 1:1 and 1:2. The drug:benzoic acid ratio of 1:2 was found to have more solubility and showed enhanced dissolution compared to pure drug. The in vitro dissolution rate of the drug:benzoic acid ratio of 1:2 was found to be more than 90 % in 60 min. Therefore, it can be concluded that the cocrystallization method with benzoic acid as coformer can be a promising approach for solubility improvement of etravirine.