Effect of mixing speed and time on dispersion of cohesive drug powder mixtures measured during dissolution
Aim: The research was conducted to study the effect of mixing parameters on the dispersion of indomethacin in cohesive powder mixtures. The extent of dispersion was estimated through a non-linear least squares modeling of drug dissolution profiles.
Method: Binary mixtures were prepared with 10% micronised indomethacin and 90% spray-dried lactose. The components were mixed at 23rpm, 49rpm and 101rpm in the Turbula T2F® mixer with samples taken at 2.5, 5, 10 and 20 minutes. Dissolution testing was undertaken in an automated dissolution apparatus using the paddle method with buffer of pH=5 as the medium. Data (6 replicates) was collected every 2 minutes over 1 hour. Statistical modeling was performed using Sigmaplot 8.0® and SPSS®.
Results: Dissolution profiles showed that the rate and extent of dissolution increased with increasing time and speed of mixing, indicating an increased dispersion within the cohesive mixtures. Dissolution data was best fitted by a sigmoidal equation and the equation parameters were estimated by non-linear least squares regression. The upper asymptote values (corresponding to the dispersion of indomethacin) and the reciprocal of the slope of the sigmoid (corresponding to the rate of dissolution) increased with mixing time and speed.
Conclusion: The study indicated that powder dispersion was related to the speed and time of mixing and that increased mixing intensity caused de-agglomeration of slowly dissolving drug agglomerates.