Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex

The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1？:？5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. 1. Introduction Any drug from a given dosage form to be absorbed must be present in the form of solution at the site of absorption. Low aqueous solubility is one of the major problems encountered during formulation development of new chemical entities especially in the process of generic product development. More than 40% of new chemical entities developed in pharmaceutical industry are practically insoluble in water. Various techniques are used for the enhancement of the solubility of poorly soluble drugs including physical and chemical modifications of drug like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, hydrotropy, cosolvency, use of surfactants, and complexation [1]. Inclusion complexes are formed by the insertion of the nonpolar molecule or the nonpolar region of one molecule into the cavity of another molecule or host molecules. The most commonly used host molecules are cyclodextrins. Cyclodextrins are nonreducing, crystalline, water soluble, cyclic oligosaccharides consisting of glucose monomers arranged in a donut-shaped