Preparation and characterization of BCS class II drugs to enhance physicochemical attributes via cocrystallization approach

Abstract

newlineCo-crystallization is now known to be one of the established methods for the improvement of physiochemical properties of drugs in pharmaceutical research and development. With the application of crystal engineering, the conversion of drug moiety into co-crystal form is getting convenient. The Motive behind this work is to convert poor water-soluble drugs into co-crystal forms with the help of various co-crystallization techniques. Techniques that were applied are mainly solvent co-crystallization, co-crystallization by slurry formation, wet milling using Dyno mill, and liquid-assisted co-grinding. Ranolazine was used as a model compound to perform Drug:Coformer crystallization, and Telmisartan (TEL) and Hydrochlorothiazide (HCT) two drug substances was screened for Drug:Drug co-crystalization. Samples obtained from various methods were evaluated by various analytical techniques like microscopy, melting point analysis, X-ray Powder Diffraction (XRPD), and dissolution study. newlineRanolazine (RAN) exhibits pH-dependent solubility, with high solubility in acidic pH and lower in basic pH. Cocrystal formation of Ranolazine (RAN) with Nicotinamide (NIC) has been synthesized and evaluated for different molar ratios (1:1, 1:2, 1:3 2:1 and 3:1). Various techniques like liquid-assisted grinding, slurry preparation and solvent evaporation were implemented to synthesize cocrystals. Conformational and characterization analysis has been performed using techniques like melting point analysis, powder X-ray diffraction and TGA. Saturation solubility of RAN alone along with cocrystals prepared in different molar ratios in buffers of different pH (1.2, 4.5 and 6.8) and water has been studied to establish enhancement in solubility. RAN cocrystals with NIC were shown to have enhanced solubility in basic pH. Utmost improvement in solubility has been observed for RAN:NIC molar ratio of 1:2. newlineTelmisartan (TEL) and Hydrochlorothiazide (HCT) fixed-dose combination is a known and effective combination for the treatment of hypertension.