Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation 2: evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols.

Three in vitro methodologies were evaluated as models for the analysis of drug release from controlled release (CR) microparticulates for inhalation. USP Apparatus 2 (dissolution model), USP Apparatus 4 (flow through model) and a modified Franz cell (diffusion model), were investigated using identical sink volumes and temperatures (1000 ml and 37 degrees C). Microparticulates containing DSCG and different percentages of PVA (0%, 30%, 50%, 70% and 90%) were used as model CR formulations. Evaluation of the release profiles of DSCG from the modified PVA formulations, suggested that all data fitted a Weibull distribution model with R2 > or =0.942. Statistical analysis of the t(d) (time for 63.2% drug release) indicated that all methodologies could distinguish between microparticles that did or did not contain PVA (Students t-test, p<0.05). However, only the diffusion model could differentiate between samples containing different PVA percentages. Similar results were observed when analysing the data using similarity and difference factors. Furthermore, analysis of the release kinetic profiles for all samples suggested the data fitted the Higuchi diffusion model (R2 > or =0.862 for the diffusion methodology data set). Due to the relatively low water content in the respiratory tract and the lack of differentiation between formulations for USP Apparatus 2 and 4, it is concluded that the diffusion model is more applicable for the evaluation of CR inhalation medicines.