Evaluation of Cefixime-Loaded Chitosan Microspheres: Analysis of Dissolution Data Using DDSolver

The objectives of this study were to fabricate cefixime-loaded chitosan microspheres with the ultimate goal of prolonging drug release and to analyze the influence of various process variables on the properties of microspheres such as mode of drug release. The cefixime-loaded chitosan microspheres were fabricated using a coacervation technique. Various process variables like volume of solvent for chitosan (glacial acetic acid), chitosan concentration, volume of phase separation agent (NaOH solution), and glutaraldehyde concentration were varied to fabricate nine different formulations. Dissolution data were evaluated using DDSolver, new software developed for the kinetic analysis of dissolution data. The microspheres were spherical, porous, and dark brown. They ranged in size from 253.13 ± 8.4 to 369.1 ± 13.7 μm, and the incorporation efficiency varied from 29.9 ± 32% to 49.3 ± 4.5%. The F5 formulation with a drug/polymer ratio of 1:3 (w/w) was the most suitable in terms of incorporation efficiency (49.3 ± 4.5%), flow characteristics (Hausner ratio = 1.4), and drug release properties. The drug release was sustained up to many hours. Fickian diffusion was the primary mode of drug release from all cefixime-loaded chitosan microsphere formulations. These results show that cefixime can be successfully microencapsulated into chitosan shells by coacervation, which is influenced significantly by formulation variables such as chitosan and glutaraldehyde concentration. INTRODUCTION Cefixime, a third-generation cephalosporin, is indicated for the management of uncomplicated urinary tract infection, otitis media, pharyngitis, tonsillitis, acute bronchitis, acute exacerbations of chronic bronchitis, and uncomplicated gonorrhea caused by susceptible strains of specific microorganisms. It inhibits the synthesis of mucopeptide in bacterial cell walls (1). The bioavailability, protein binding, and half-life of cefixime are approximately 50%, 60%, and 3 h, respectively. These properties require the administration of large doses (400 mg in two divided doses for up to 5–7 days) of cefixime to achieve and then maintain therapeutic levels (2). The fabrication of a cefixime-loaded, sustained-release formulation would be useful as compared to the current dose regimens. Consequently, the aim of this study was to develop a slow-release formulation of cefixime. For this purpose, microencapsulation and chitosan were selected as the technique and polymer (release-retardant material), respectively. Microencapsulation, which is the application of a thin polymeric coating to individual core substances (particle size range 5–5000 μm), is extensively employed in various pharmaceutical applications, like prolonging drug release to improve bioavailability (3). The coacervation technique, one of the most commonly adopted and uncomplicated methodologies of microencapsulation, has been employed to develop microspheres of a range of compounds using various polymers (4). Currently, various studies (5–9) have been proposed using chitosan as a rate-controlling and sustaining polymer as it is substantially beneficial in fabricating biodegradable microspheres. Chitosan, a natural biopolyaminosaccharine (10), is a weak base (11) and is soluble in dilute aqueous acidic solutions like 2% acetic acid solution (12). The presence of a free amino group is helpful for bonding with drugs substances and controlling their release (13). A convenient way to synthesize chitosan microspheres is the coacervation method with the use of glutaraldehyde as a cross-linking agent (14). A literature survey showed no studies involving the formulation and characterization of microspheres using cefixime. Thus, the primary objective of this study was to fabricate cefixime-loaded chitosan microspheres (CLCM) and secondarily to investigate various combinations of excipients such as acetic acid and NaOH solutions, drug– polymer relationships, and glutaraldehyde concentrations. These formulation variables may influence the characteristics of microspheres. Moreover, considerable attention was focused on the dissolution analysis of CLCM fabricated in these studies because in vitro dissolution analysis of solid oral formulations is an essential tool of dosage form development and quality control testing of drug release *Corresponding author. diss-19-02-03.indd 13 5/18/2012 8:03:21 PM dx.doi.org/10.14227/DT190212P13