Acta Pharm. 59 (2009) 121-132
Original research paper
Ternary complexation of carvedilol, β-cyclodextrin and citric acid for mouth-dissolving tablet formulation
VARSHA POKHARKAR, ABHISHEK KHANNA, VINOD VENKATPURWAR, SHEETAL DHAR and LEENATA MANDPE
Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune-411038, Maharashtra, India
Accepted March 11, 2009
The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with β-cyclodextrin and citric acid and to formulate its mouth-dissolving tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from ther buccal cavity. Phase solubility studies revealed the ability of β-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with β-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable.
Keywords: carvedilol, cyclodextrin, citric acid, ternary complex, solubility, spray drying, mouth-dissolving tablet