Solubility and bioavailability enhancement of poorly water soluble APIs for cost effective formulation

Abstract

The present research work attempted to improve the oral bioavailability of the antiviral drug newlineEfavirenz (EFV) using a pharmaceutical cocrystallization technique. EFV comes under BCSII newlineand has extremely low water solubility and results in low oral bioavailability. The Hansan newlinesolubility parameter, and#916;pKa value, thermal method, and virtual interaction techniques were newlineutilized for the screening of plausible coformer. During the screening stage, we evaluated newlinecoformers like malic acid, mannitol, caffeine, glutaric acid, tyrosine, arginine, and newlinenicotinamide with various stoichiometric ratios. Amongst the tested coformer, we got the newlinecocrystal with nicotinamide, caffeine, and glutaric acid. Based on the results of analytical newlinecharacterization, solubility, and in- vitro dissolution studies NICO, a water-soluble, safe, nontoxic newlinevitamin B3 was selected for further study. The EFV and nicotinamide (NICO) were newlineselected in a (1:1) stoichiometric ratio and efavirenz nicotinamide cocrystal (ENCOC) was newlineprepared through the liquid-assisted grinding method (LAG) and spray drying techniques. The newlineconfirmation of the formation of a new solid phase was done through spectroscopic techniques newlinelike Fourier transmission infrared (FTIR), Raman, and 13C solid-state nuclear magnetic newlineresonance (13C ssNMR). Thermal techniques like differential scanning calorimetry (DSC), newlinethermogravimetric analysis (TGA), and hot stage microscopy (HSM) illustrated the thermal newlinebehavior and melting patterns of ENCOC, EFV, and NICO. The X-ray powder diffraction newline(XRPD) confirms the formation of a new crystalline phase in ENCOC and ENCOCSD. The newlineMorphology was determined through scanning electron microscopy (FESEM). The results of newlinesaturated solubility studies and In-vitro drug release studies exhibited an 8.9-fold enhancement newlinein solubility and a 2.56-fold enhancement in percentage cumulative drug release. The newlinepercentage drug content of ENCOC was found higher than 97% and cocrystal exhibits excellent newlineaccelerated s