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

ABSTRACT

Drug-cyclodextrin complexes improve aqueous solubilityand dissolution rate of poorly water-soluble drugs.Solubilisation followed by buccal delivery of poorlywater-soluble drugs can be advantageous for increasingdrug absorption. Darifenacin is an antispasmodic usedagainst urinary incontinence and specifically blocksM3 muscarinic acetylcholine receptors in smoothmuscle. M3 receptors are mainly located in exocrineglands, smooth muscle and vascular endothelium. Theoral absorption of darifenacin is poor owing to its lowsolubility. It also has poor bioavailability (15-19%) dueto a high rate of first-pass metabolism. Complexationwith beta-cyclodextrin was carried out to enhancesolubility. The best results were obtained by co-grindingin a 11 molar ratio of drug ?-cyclodextrin. The solidinclusion complexes were characterized by DSC, X-raydiffractometry and FTIR. Inclusion complexes showedhigher dissolution rates than the pure drug. Controlledreleasemucoadhesive patches were prepared with twohydroxypropyl methylcellulose (HPMC) polymers,K100M CR and K15. The patches were assessed forsurface pH, folding endurance, swelling, mucoadhesiveproperties, in-vitro residence time, vapor transmissiontest and in-vitro (cellophane, egg membrane) and exvivo(goat buccal mucosa) release. Formulations Ha2(2%) HPMC K100M CR and Pa4 (4%) HPMC K15showed good mucoadhesive strength, in-vitro and exvivoresidence times, with controlled release for 10hours.