title: Controlled release chitosan microspheres of mirtazapine: in vitro and in vivo evaluation.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104, Karnataka, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Ranjan
authors.forename: Gopal Venkatesh
authors.initials: GV
authors.lastname: Shavi
authors.forename: Usha Yogendra
authors.initials: UY
authors.lastname: Nayak
authors.forename: Karthik
authors.initials: K
authors.lastname: Arumugam
authors.forename: Ranjith Kumar
authors.initials: RK
authors.lastname: Averineni
authors.forename: Sreenivasa Reddy
authors.initials: SR
authors.lastname: Meka
authors.forename: Pandey
authors.initials: P
authors.lastname: Sureshwar
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D055598:Chemical Phenomena; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D005976:Glutaral / Q000737:chemistry; D006207:Half-Life; D006358:Hot Temperature; D007273:Injections, Intramuscular; D008297:Male; D008657:Metabolic Clearance Rate; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D000078785:Mirtazapine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000929:Antidepressive Agents, Tricyclic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D008803:Mianserin; D048271:Chitosan; D000078785:Mirtazapine; D005976:Glutaral