Microencapsulation of chlorpheniramine maleate-resin particles with crosslinked chitosan for sustained release.

Formulation and preparation parameters of drug/ion-exchange particles microencapsulated in cross-linked chitosan were evaluated for controlled release of the water-soluble drug chlorpheniramine maleate (CPM) in a suspension. An emulsion solvent evaporation method was used to produce CPM-resinates embedded in glutaraldehyde (GTA) crosslinked chitosan microspheres (MCSs). Crosslinking extent in the chitosan was monitored by swelling measurements. Controlled release was evaluated by dissolution tests in simulated gastric fluid without enzyme (SGF) and in simulated intestinal fluid without enzyme (SIF). CPM-resinates contained 62% (w/w) of drug. MCSs were spherical, ranging from 82 to 420 microns in diameter, and contained multiple resinates. The sizes of MCSs prepared with safflower oil and Span 80 were controlled by surfactant concentration, stirring speed, and duration of stirring. Maximum crosslinking was produced with 240 mg GTA per 250 mg of chitosan. Maximum drug release from free CPM-resinates was about 60% by 1 hr in SGF, and was about 100% by 3 hr in SIF. CPM release was slower from MCSs crosslinked with 120 mg of GTA compared to 5 mg GTA in both media. By 8.3 hr, the more crosslinked MCSs released about 30% CPM in SGF, and about 60% in SIF. Because of the apparent ceiling on release in SGF, the final experiments were conducted in SIF. Increasing the weight ratio of the chitosan coating to CPM-resinate ratio from 1:1 to 4:1 moderately decreased release profiles carried out to 33 hr. Increasing MCS diameters from 82 to 163 microns moderately decreased release profiles. Microencapsulation of CPM-resinates with crosslinked chitosan demonstrated controlled release of CPM in SGF and SIF without enzymes. The retardation effect increased when the crosslinking extent and chitosan to resin ratio increased.