Mucoadhesive microspheres

Nasal delivery protects drugs like salbutamol sulphate (SS) from hepatic first-pass metabolism. The study aimed to formulate mucoadhesive sodium alginate (SA) microspheres loaded with (SS) by emulsion cross-linking, with mucoadhesive polymers, for potential nasal delivery by-passing first-pass metabolism. Relevant physichochemical properties, in vitro release and irritation in rabbits were investigated. Stirring rate and cross-linking time affected microsphere parameters. Microspheres were spherical in shape, discrete, with smooth and porous properties favorable for intranasal absorption with high drug-loading of 78.7 %. Mixed-polymers microspheres exhibited higher degree of swelling. Kinetic analysis of release data showed a case II release kinetics for alginate microspheres, and anomalous mechanism for other mixed-polymers formulae. Pronounced sustained drug release over 8 hours was exhibited upon incorporation of Carbopol® 934 and Hydroxypropyl methyl cellulose. The formulated microspheres showed high swelling ability and good mucoadhesion, offering a good potential for future in vivo study to confirm safety and avoidance of first-pass metabolism.

  Diltiazem hydrochloride, a calcium channel blocker, is widely used for the treatment of angina pectoris, hypertension and arrhythmias. The usual dose of diltiazem hydrochloride is 180-240 mg/day. The conventional tablet or capsule is administered 3 or 4 times a day due to its low biological half-life of about 3.7 h. The problems of frequent administration and variable low bioavailability (36-50%) after oral administration of conventional tablet or capsules have been attenuated by designing diltiazem hydrochloride in the form of mucoadhesive microspheres. Diltiazem hydrochloride loaded mucoadhesive microspheres were successfully prepared by emulsification-internal gelation technique with a maximum encapsulation efficiency of 99.48± 0.32%.The order of increasing release rate observed with various microspheres was as follows Sodium alginate < Sodium alginate+ NaCMC < Sodium alginate+ HPMC. The order of increasing release rate observed with various cross linking agents was as follows Aluminum chloride < Barium chloride< Calcium chloride. The release behaviour of microspheres, with different cross-linking agents depends upon the valency and size of the cations of the respective cross-linking agent. The dissolution profiles follow zero order kinetics and the mechanism of drug release was governed by peppas model. The in vitro wash-off test indicated that the wash-off was faster at simulated intestinal fluid (phosphate buffer, pH 7.4) than that at simulated gastric fluid (0.1 M HCl, pH 1.2). The mucoadhesive microspheres formulated with sodium alginate+HPMC and calcium chloride showed a satisfactory sustained release profile for 12 hours.