Optimization of Transmucosal Buccal Delivery of Losartan Potassium using Factorial Design

Abstract:

Objective: Buccal delivery is considered to be an important alternative to the peroral route for the systemic administration of drugs. Losartan potassium is an angiotensin II receptor antagonist with an oral bioavailability of only 33% due to extensive first pass metabolism. Methodology: Mucoadhesive buccal films of losartan potassium were prepared using solvent casting method with hydroxyl propyl methyl cellulose HPMC K100M and xanthan gum as retardant polymers xanthan gum and plasticizer as propylene glycol. FTIR analysis of drug and excipients binary mixtures showed no interactions. The films were subjected to physical investigations such as uniformity of thickness, weight, drug content, folding endurance, surface pH and mucoadhesive strength. Results: Flexibility of films were dependent on polymer and plasticizer concentration. The mucoadhesive force and swelling index was higher for formulations containing higher percentage of HPMC K100M. Ex vivo permeation studies revealed that all films exhibited sustained release in the range of 63.75 ± 1.08% to 89.95 ± 1.24 % for a period of 7 h. Ex vivo permeation studies through sheep buccal mucosa indicated that films containing higher percentage of the mucoadhesive polymer (HPMC K100M) showed higher permeation of the drug for duration of 6-7 h. Conclusion: Mucoadhesive buccal films of losartan potassium were successfully prepared and offers a promising alternative to oral delivery.

Key words: Losartan potassium, HPMC K100M, Xanthan gum, Buccal mucosa, Mucoadhesive, Permeation.