(134a) Mixing Time Determination in a Vessel with Rotating Basket (USP Dissolution Testing Apparatus 1)

The USP Apparatus 1 (rotating basket) has become a preferred dissolution testing tool to evaluate the dissolution performance of pharmaceutical oral solid dosage forms and to determine drug formulations with different drug release profiles. In general, samples are taken at a specified midway position inside the dissolution media volume during the dissolution testing process to obtain the dissolution profile. The profile represents the amount of the active drug released from its dosage form over time. Therefore, of significant importance during the dissolution process is the mixing time determination, i.e., the time needed for the drug substance released from the dosage form to become dispersed throughout the vessel and especially at the sampling location. The objectives of this work are to experimentally and computationally evaluate the blend time in the USP Apparatus 1 under different operating conditions, i.e., basket mesh size, liquid fill volume, and agitation speed. Experimentally, a non-intrusive discoloration method coupled with image processing using MATLAB was conducted. Time-dependent simulations using the Lattice Boltzmann Method combined with Large Eddy simulation were additionally performed to computationally predict mixing time. Our results show that mixing time is a strong function of the basket mesh size, agitation speed, and liquid fill volume. The experimental and predicted mixing time results were in substantial agreement and, thus, fitted with a correlated equation developed for the USP 1 system. Our study could be helpful for practitioners in selecting appropriate dissolution testing as well as operating conditions, especially when the samples are removed from the medium to obtain dissolution profiles.