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
vbpokharkar@yahoo.com.in
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