Development of Buccal Patches for Delivery of Darifenacin from Beta-Cyclodextrin Complexes

Abstract

Drug-cyclodextrin complexes improve aqueous solubility and dissolution rate of poorly water-soluble drugs. Solubilisation followed by buccal delivery of poorly water-soluble drugs can be advantageous for increasing drug absorption. Darifenacin is an antispasmodic used against urinary incontinence and specifically blocks M3 muscarinic acetylcholine receptors in smooth muscle. M3 receptors are mainly located in exocrine glands, smooth muscle and vascular endothelium. The oral absorption of darifenacin is poor owing to its low solubility. It also has poor bioavailability (15-19%) due to a high rate of first-pass metabolism. Complexation with beta-cyclodextrin was carried out to enhance solubility. The best results were obtained by co-grinding in a 1:1 molar ratio of drug: β-cyclodextrin. The solid inclusion complexes were characterized by DSC, X-ray diffractometry and FTIR. Inclusion complexes showed higher dissolution rates than the pure drug. Controlledrelease mucoadhesive patches were prepared with two hydroxypropyl methylcellulose (HPMC) polymers, K100M CR and K15. The patches were assessed for surface pH, folding endurance, swelling, mucoadhesive properties, in-vitro residence time, vapor transmission test and in-vitro (cellophane, egg membrane) and exvivo (goat buccal mucosa) release. Formulations Ha2 (2%) HPMC K100M CR and Pa4 (4%) HPMC K15 showed good mucoadhesive strength, in-vitro and exvivo residence times, with controlled release for 10 hours.

Keywords

• Darifenacin
• Cyclodextrin
• Complexation
• Buccal
• Patch