Abstract
The supercritical assisted atomization (SAA) was proposed as a new technique to produce composite microparticles for drug controlled release. Ampicillin trihydrate and chitosan were selected as model drug and carrier, respectively, and 1% v/v acetic acid aqueous solution was used as solvent. The effect of the polymer/drug ratio on particle morphology and drug release rate was evaluated. SEM analysis indicated that non‐coalescing spherical microparticles formed by chitosan/ampicillin were produced by SAA. All coprecipitates produced have a sharp particle distribution, with diameters ranging between about 0.1 and 6 µm. SAA composite microparticles were characterized by X‐ray, DSC, EDX and UV‐vis analysis. A solid solution of the chitosan and ampicillin was produced and a stabilizing effect of the polymer on the drug has resulted that protects ampicillin from thermal degradation. A prolonged release from SAA coprecipitates with respect to raw drug and physical mixtures of chitosan and ampicillin was obtained; moreover, the polymer/drug ratio has revealed to be a controlling parameter for drug release. Drug release mechanisms characteristic of swelling‐controlled systems were observed, with ampicillin release depending on both relaxation and diffusive mechanisms. An empirical binomial equation was used to describe experimental data, showing a fair good agreement with ampicillin release data if both the relaxational and the diffusional parameters are function of the polymer/drug ratio. Biotechnol. Bioeng. 2007; 97: 1626–1637. © 2007 Wiley Periodicals, Inc.