Studies on Development of Controlled Release Matrix Tablets of Camptothecin-An Anticancer Drug

Abstract

Abstract: Objectives: The present investigation was carried out with an objective of formulating prototype controlled release (CR) matrix tablets of Camptothecin (CPT), an anti-cancer drug. Experimental: pH solubility profile studies of CPT and solubility of CPT in different surfactants were carried out. Controlled release tablets were prepared by direct compression method using hydroxyl propylmethyl cellulose (HPMC LVCR and HPMC K4M) as release retardants. The effect of different grades of microcrystalline cellulose (MCC) like Avicel PH 101 and Avicel PH 105 and solubilizing agents like cyclodextrins were included in the formulations and their effect on CPT release from tablets were studied. Results and Discussion: Solubility studies were conducted in order to select suitable dissolution medium for CPT. Based on the solubility studies, 0.1N HCl with 3% w/v SLS (pH1.2) was selected as dissolution medium. The FTIR and DSC results indicated that there was no in situ interaction between CPT and the selected excipients in the formualtions. Formulations containing 20% w/w of hydroxypropyl-β-cyclodextrin with Avicel PH105 as filler and HPMC k4M as release retardant gave superior CPT release of 98.40 ± 1.02% at the end of 12 h and fulfilled the regulatory requirements. The Higuchi square root model showed higher correlation coefficient values (0.949-0.990) indicating diffusion was the release mechanism for CPT from tablets. Conclusion: CPT can be formulated in to CR matrix tablets using HPMC K4M as release retardant and MCC as filler for better therapeutic efficacy. Key Words: Camptothecin, CR matrix tablets, Cyclodextrins, Dissolution studies, Solubility studies.