Formulation of Candisartan Mucoadhesive Buccal Tablets After Improving the Solubility by Solid Dispersion and Inclusion Complex Methods.

Abstract

This research work aimed to develop and evaluate the buccal tablets of Candesartan using various Mucoadhesive polymers viz. Hydroxy Propyl Methyl Cellulose (HPMC K4M), Sodium Carboxy methyl cellulose (Sodium CMC), Sodium alginate individually and in combination. Candesartan is an angiotensin II receptor blocker (ARB) used in the treatment of hypertension. It shows the oral bioavailability of 15% due to the first-pass metabolism and has a biological half-life of approximately 9hrs. It is poorly absorbed after oral administration, and having poor solubility and wettability leads to poor dissolution. The solubility and dissolution rate were improved by preparing solid dispersions using Poloxamer 188 by melt agglomeration (MA), and inclusion complexes were made with β-Cyclodextrin (β-CD) by kneading method. The tablets were prepared by direct compression method using selected mucoadhesive polymers loaded with drug, free (or) in drug carrier combination and were characterized by swelling studies, ex vivo, and in vivo mucoadhesive time, ex vivo Mucoadhesion force, in-vitro drug release studies. Based on the in vitro drug release data, the formulations containing the two drug-carrier combinations, Poloxamer 188 (MA 1:2) and β-CD (1:1 M), were selected optimized formulations. As per the X ray Diffraction studies drug and excipients are compatible with each other, solubility profile improvement was confirmed by increasing dissolution studies. Using solid dispersion and inclusion complexes methods, the drug’s wettability and dissolution profiles were improved.