Controlled release chitosan microspheres of mirtazapine: in vitro and in vivo evaluation.

The purpose of the study was to formulate and evaluate controlled release chitosan microspheres of mirtazapine (MTZ) to improve the bioavailability by altering the pharmacokinetic profiles of the drug. Chitosan microspheres were prepared to prolong the release of the drug into the systemic circulation. Microspheres were prepared by a single water in oil (w/o) emulsion technique varying the chitosan/drug ratio, stirring speed and concentration of the crosslinking agent (glutaraldehyde). Drug-polymer compatibility studies were carried out using fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The microspheres were evaluated for encapsulation efficiency, particle size, surface morphology, swelling index, in vitro release, as well as erosion and in vivo studies in rats. The FT-IR and DSC studies revealed no interaction between drug and polymer. The encapsulation efficiency of different formulation varied from 53 ± 1.2% to 78 ± 1.5%. The mean particle size of the optimized formulation F-14 was 106.4 ± 0.5 µm. Surface morphology revealed that chitosan microspheres were discrete and spherical in shape with a porous surface. The release of MTZ from chitosan microspheres was rapid up to 4 h, and then it was continuously and slowly released up to 48 h. Optimized formulation (F-14) was found to be stable under accelerated storage conditions based on International Conference on Harmonisation guidelines. Pharmacokinetic studies revealed that the optimized formulation showed significant increases in systemic exposure (AUC = 177.70 ± 7.39 µg·h/mL), half-life (4.72 ± 0.46 h) and reduced clearance (0.009 ± 0.0001 L/h) compared to pure drug administration. Hence, the present study demonstrates that controlled release formulation of MTZ microspheres using chitosan can improve pharmacokinetic profiles of MTZ.

Multiparticulate drug delivery system of aceclofenac: development and in vitro studies.

The aim of this study was to develop an enteric-coated multiunit dosage form containing aceclofenac, a nonsteroidal anti-inflammatory drug. The pellets were prepared by using extrusion/spheronization method, and the core pellets were coated with a pH-sensitive poly(meth) acrylate copolymer (Eudragit L100-55) to achieve site-specific drug release. The formulated pellets were characterized for percentage yield, size distribution, surface morphology studies, drug content, and flow properties. In vitro dissolution test was used for comparison of drug release profiles of various coated pellets. The practical yield was found to be 90-95%. The particle size of enteric-coated pellets was found to be in the range of 0.59-0.71 mm. The pellets were spherical in shape and surfaces of pellets were found to be rough and showing micropores. Enteric-coated pellets showed good flow properties and in vitro dissolution profile. Dissolution tests were carried out in a USP type II dissolution apparatus in media-simulating pH conditions of the gastrointestinal tract. The release of the aceclofenac from formulated pellets was established to be minimum in the pH 1.2 (<5%) for a period of 2 h, and at pH 6.8, it shows the maximum release (85 +/- 5% release within 1 h) which indicates gastric resistance of the formulated pellets. The 20% wt/wt enteric-coated pellets were compared to that of marketed product (tablets), it was observed that pellets showed better release profile. The study concluded that the formulated multiparticulate dosage forms can be used as an ideal drug delivery system for the aceclofenac.