Development and validation of an in vitro release method for topical particulate delivery systems.

The aim of this study was to develop an in vitro release method for topical particulate delivery systems using the immersion cell in combination with paddle dissolution apparatus. Chitosan- and methacrylate-based microparticles with mupirocin were prepared and used as model topical delivery systems for method development. Diffusion of the drug occurred across a mixed cellulose ester membrane, which demonstrated low drug adsorption and low diffusional resistance. After an initial lag phase the amount of drug released became proportional to the square root of time. The method was discriminative toward differences in formulation, as well as toward differences in drug concentration inside the sample compartment. The method was further used to confirm sameness between batches of the same composition prepared by the same process. Variations in paddle rotation speed (25 rpm, 50 rpm, 100 rpm), paddle height (1cm, 2.5 cm) and volume of release medium (100ml, 200 ml) did not significantly alter the release rates. The method of analysis was validated according to ICH guidelines. Currently there are no compendial or standard methods and apparatuses for in vitro release testing of topical microparticles. The developed method can be a useful guide in formulation development of such delivery systems.

Physico-chemical characterization and the in vitro genotoxicity of medical implants metal alloy (TiAlV and CoCrMo) and polyethylene particles in human lymphocytes.

BACKGROUND: The main objective of the present study was to investigate chemical composition and possible cyto/genotoxic potential of several medical implant materials commonly used in total hip joint replacement. METHODS: Medical implant metal alloy (Ti6Al4V and CoCrMo) and high density polyethylene particles were analyzed by energy dispersive X-ray spectrometry while toxicological characterization was done on human lymphocytes using multi-biomarker approach. RESULTS: Energy dispersive X-ray spectrometry showed that none of the elements identified deviate from the chemical composition defined by appropriate ISO standard. Toxicological characterization showed that the tested materials were non-cyto/genotoxic as determined by the comet and cytokinesis-block micronucleus (CBMN) assay. Particle morphology was found (by using scanning electron and optical microscope) as flat, sharp-edged, irregularly shaped fiber-like grains with the mean particle size less than 10µm; this corresponds to the so-called "submicron wear". The very large surface area per wear volume enables high reactivity with surrounding media and cellular elements. CONCLUSIONS: Although orthopedic implants proved to be non-cyto/genotoxic, in tested concentration (10µg/ml) there is a constant need for monitoring of patients that have implanted artificial hips or other joints, to minimize the risks of any unwanted health effects. GENERAL SIGNIFICANCE: The fractal and multifractal analyses, performed in order to evaluate the degree of particle shape effect, showed that the fractal and multifractal terms are related to the "remnant" level of the particles' toxicity especially with the cell viability (trypan blue method) and total number of nucleoplasmic bridges and nuclear buds as CBMN assay parameters.