Mechanistic modelling and mechanistic monitoring: simulation and shadowgraph imaging of particulate dissolution in the flow-through apparatus.
Accurate mechanistic modelling of a complex system requires insight into the process being simulated, in addition to a theoretical 'first-principles' approach. The current work uses a numerical mechanistic model to simulate dissolution of a particulate system in the flow-through dissolution apparatus. A shadowgraph imaging method is also used to monitor the dissolution process, providing real-time estimates of particle motion, number and total dissolution time. Experimental dissolution studies of ibuprofen particles are used to assess the accuracy of the model. The numerical model adequately predicts the ibuprofen particle dissolution rate at 16 mL min(-1) . Parameter sensitivity analysis identified dissolution test circumstances requiring more, or less, accuracy in the particle size and density calculations. The shadowgraph imaging method successfully determined the total dissolution time and decreasing particle numbers over time. The images confirmed the pulsing particle motion of the numerical model but revealed some more complex velocity patterns, assisting numerical model development. Further optimisation of the sampling window is required to capture all relevant particle motion and changing particle size distribution. A mechanistic model can successfully simulate particulate dissolution in the flow-through apparatus, and when used along with shadowgraph imaging, can give valuable insight into the dissolution process mechanisms and environment.
D'arcy
Deirdre M
DM
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland. ddarcy@tcd.ie
Persoons
Tim
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation*; D003198:Computer Simulation; D007052:Ibuprofen / Q000032:analysis*; D010316:Particle Size; D010602:Pharmacopoeias as Topic; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D007052:Ibuprofen