Numerical simulation of capsule dissolution in the USP apparatus II.

摘要

The capsule is the second most common type of drug dosage form, yet detailed research of capsule dissolution in the USP Apparatus II (a paddle dissolution apparatus that mimics the drug dissolution process in an in vivo environment) is not well reported. In this work, a mathematical model was developed that incorporates both the dissolution of the capsule shell and the slug within the capsule shell. Capsule shell dissolution was modeled with the assumption that the shell undergoes an erosion process only. The capsule slug dissolution model incorporated mass transfer principles, Markov chain theory, and the influence of hydrodynamics on capsules dissolution using computational fluid dynamics (CFD)-predicted velocity profiles. To complete the model, the mass transfer coefficients (determined experimentally and theoretically) were incorporated. The model was validated by statistically comparing the simulated profiles to the experimental data using the similarity factor. In addition, this model can provide insights into the dissolution mechanism where a drug product may either disintegrate or erode during dissolution testing. This capsule slug dissolution model has the potential to reduce substantially the number of time-consuming physical dissolution experiments and maximize the efficiency of process development.