Send Orders for Reprints to reprints@benthamscience.net 154 Current Drug Discovery Technologies, 2014, 11, 154-161 Cyclodextrin Inclusion Complex of Racecadotril: Effect of Drug-- Cyclodextrin Ratio and the Method of Complexation Mona Semalty 1 , Mitali Panchpuri 1 , Devendra Singh 2 and Ajay Semalty 1,* 1 Department of Pharmaceutical Sciences, H.N.B. Garhwal University, Srinagar (Garhwal)-246174, Uttarkhand, India; 2 Department of Chemistry, H.N.B. Garhwal University, Srinagar (Garhwal)-246174, Uttarkhand, India Abstract: Racecadotril is an antisecretory and antidiarrheal agent against watery diarrhoea in children. Racecadotril is a class II drug (as per Biopharmaceutical Classification System) with poor aqueous solubility and dissolution rate limited absorption. -cyclodextrin complexation of solubility or dissolution rate limited drugs provides an amphiphilic complex with improved solubility and dissolution profile. Thus Racecadotril – -cyclodextrin complex were prepared to improve its solubility and dissolution by imparting an environment of improved hydrophilicity. Racecadotril was complexed with -cyclodextrin (in 1:1 and 1:2 molar ratios) by two different methods (solvent evapora- tion and kneading method). These inclusion complexes were evaluated for solubility, drug content, scanning electron mi- croscopy (SEM), differential scanning calorimetry (DSC), X ray powder diffraction (XRPD) and in vitro dissolution study. The highest drug content (30.83%) was found in complex made by kneading method (RK1:1) in 1:1 molar ratio. Complex prepared by solvent evaporation method (RSE1:1, RSE1:2) were found to be showing irregular disc shaped non-porous surface, while the complexes prepared by kneading method (RK1:1, RK1:2) showed rough, fluffy, non-porous and irregu- lar surface in SEM. Solubility of the drug improved up to 2 to 3 folds in the complexes. The complex RK1:1 showed the greatest improvement in solubility (from 28.98 to76.56 μg/ml). The dissolution of the complexes was also found to be im- proved. Complex prepared by solvent evaporation method in 1:1 molar ratio (RSE1:1) showed a marked improvement in percent drug release (100.33%) than that of pure drug (52.58%) at the end of 1 hour in dissolution study. FTIR, DSC and XRPD data confirmed the formation of inclusion complex. It was concluded that water solubility of all the complexes were increased when the drug was complexed with -CD in 1:1 molar ratio. The complex made in 1:1 molar ratio (irrespective of the method) showed better solubility and the dissolution profile as compared to the complex made in 1:2 molar ratio. It was concluded that the complex prepared by the solvent evaporation method showed better solubility and the dissolution due to better amorphization of the drug. Keywords: BCD complex, in vitro dissolution, Racecadotril, solubility. 1. INTRODUCTION The solubility of a drug is one of the most critical factors in developing a drug into a dosage form or delivery system. The aqueous solubility governs the amount of compound that will dissolve and hence the amount available for absorption. Therefore, a fair solubility in gastro intestinal medium is an indispensable property for good bioavailability of orally ad- ministered drugs. Dissolution and solubility are the two im- portant properties which play an important role in formula- tion development of the drugs [1, 2]. Poor solubility and the dissolution of drugs is the major challenge for formulation scientists. Various techniques like solid dispersion, solvent deposition, micronization etc. have been investigated for resolving solubility issue in pharmaceutical product devel- opment. Each of these techniques has its own merits and demerits. Out of these, the complexation technique has been *Address correspondence to this author at the Department of Pharmaceuti- cal Sciences, H. N. B. Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India; Tel: +91 1370 267395; Fax: +91 1346 252174; E-mail: semaltyajay@gmail.com employed more precisely to improve the solubility and the dissolution of poorly water soluble drugs [3-10]. Complexation is generally defined as the reversible asso- ciation of a substrate and ligand to form a new species. Cy- clodextrins (CDs) are classic examples of compounds that form inclusion complexes. These complexes are formed when a ‘‘guest’’ molecule is partially or fully included inside a ‘‘host’’ molecule (e.g. CD) with no covalent bonding. When inclusion complexes are formed the physicochemical parameters of the guest molecule are disguised or altered and improvements in the molecule’s solubility, stability, taste, safety, bioavailability, etc., are commonly seen. Cyclodextrins are the cyclic carbohydrates formed during the bacterial (Bacillus macerans) degradation of cellulose and used as the potential complexing agents to form inclu- sion complex with poorly water soluble drugs. These are amphiphilic molecules (cyclic oligosaccharides) consist of (-1,4) linked -D-glucopyranose units with lipophilic cen- tral cavity and a hydrophilic outer surface. The 3D structure of the parent CD provides a cavity that is hydrophobic rela- tive to an aqueous environment. Cyclodextrins are shaped 1875-6220/14 $58.00+.00 © 2014 Bentham Science Publishers