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 1:1 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.
ABSTRACT
Roots of the plant Inula racemosa are used as folk medicine in east Asia and Europe. Inula racemosa in combination with Commiphora mukul was reported to cure myocardial ischemia. However, systematic investigation of the plant for its specific role in heart diseases has not been conducted so far. In the present study, we have reported the isolation of four major constituents A, B, C and D along with some minor constituents from the plant Inula racemosa. Among the major constituent, constituent Dhas been selected first from spectral data and studied for its cardiac activity on isolated frog heart. The experimental data show that constituent D decreases heart rate and force of contraction at 40 mcg/ml. Actions of Adrenaline are blocked by constituent D and it also acts as an agonist for Propranolol. The studies indicate that constituent D produces a negative ionotropic and negative chronotropic effect on frog's heart. These studies can be utilized as a cardiac marker for exploring the cardiac activity of the plant Inula racemosa.
