Utility of Mannitol and Citric Acid for Enhancing the Solubilizing and Taste Masking Properties of β-Cyclodextrin: Development of Fast-Dissolving Tablets Containing Extremely Bitter Drug

Introduction Development of Fast dissolved tablets (FDTs) in which taste is masked, and drug dissolution is improved, is a major challenge especially in case of extremely bitter drug with poor water solubility such as aceclofenac. Purpose The purpose of this study was to enhance the taste masking and solubilizing properties of beta-cyclodextrin using citric acid and mannitol through preparation of acid soluble taste masked granules of aceclofenac (ASTMGA). Methods General factorial design was applied to optimize FDTs containing ASTMGA so to have short disintegration time (< 30 sec.), acceptable taste and enhanced drug dissolution in gastric fluid. Three formulation variables; the type of sugar/cellulose based diluents, X-1 (Galen IQ (R) and Prosolv (R)), superdisintegrant type, X-2 (Crospovidone (R), Glycolys (R) and Ac-Di-Sol (R)) and superdisintegrant concentration, X-3 (10 % and 20 %) were included in the design. The systems were assessed for hardness, friability, in vitro disintegration, wetting time, in vitro dissolution and in vivo oral study. Results The combination of Prosolv (R) and Crospovidone (R) in the formulation of FDT gave optimum disintegration time. The stability of the optimized FDT in different package materials was retained after storage at 40 degrees C/75% RH for six months. Contrary to FDT containing conventional aceclofenac beta-cyclodextrin inclusion complex, FDT containing ASTMGA showed highest dissolution rate in both simulated salivary and gastric fluids and excellent ability to mask the bitterness of drug. Conclusions Our results propose that the combination of citric acid, mannitol and beta-cyclodextrin could be promising to improve taste masking and solubilizing properties of beta-cyclodextrin.