Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation.
The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with beta-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 the buccal cavity. This would help to overcome its first-pass metabolism and thereby improve bioavailability. Phase solubility studies revealed the ability of beta-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with beta-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.
Pokharkar
Varsha
V
Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune-411038, Maharashtra, India. vbpokharkar@yahoo.co.in
Khanna
Abhishek
A
Venkatpurwar
Vinod
V
Dhar
Sheetal
S
Mandpe
Leenata
L
D000278:Administration, Buccal; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005079:Excipients; D011412:Propanolamines; D013607:Tablets; D047392:beta-Cyclodextrins; D000077261:Carvedilol; D019343:Citric Acid