Dissolution of a poorly water-soluble drug dry coated with magnesium and sodium stearate.
The purpose of this research was to investigate the influence of dry coating micronized cohesive powders of a poorly water-soluble drug, indomethacin with force control agents, on its dissolution performance. A dry mechanical fusion method (mechanofusion) was used to coat indomethacin powders with magnesium stearate (0.25%,1%,5%) and sodium stearate (5%). After mechanofusion, significantly increased bulk and tapped densities and decreased intrinsic cohesion were observed for all samples. X-ray photoelectron spectroscopy analysis confirmed that a thicker magnesium stearate surface coating was achieved with increasing concentrations of the material. Dissolution was studied using the USP paddle method in buffer pH 5.0; several modelling approaches were used to explore the dissolution mechanisms. Whilst the bi-exponential equation represented dissolution of mechanofused indomethacin powders occurring from dispersed and agglomerated particles, it provided unrealistic parameter estimates for the two coating materials of contrasting properties. Initial increases in indomethacin dissolution were dependent on the concentration of magnesium stearate mechanofused onto the drug powders. The dissolution enhancing effect of indomethacin powders mechanofused with 5% sodium stearate was attributed to its surfactant properties that increased dispersion of indomethacin agglomerates. Initial drug release from the coated powders was described by a matrix-diffusion system according to the Higuchi model.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, Australia.
Tracy
T
Tay
David A V
DA
Morton
Thomas R
TR
Gengenbach
Peter J
PJ
Stewart
D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry*; D008956:Models, Chemical; D056951:Photoelectron Spectroscopy; D011208:Powders; D013229:Stearic Acids / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
D005079:Excipients; D011208:Powders; D013229:Stearic Acids; D013501:Surface-Active Agents; C031183:stearic acid; D007213:Indomethacin