(657a) Prediction of Tablet Dissolution By Process Parameters in Continuous Manufacturing
AIChE Annual Meeting
2017 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Critical Quality Attribute Monitoring and Control in Pharmaceutical Manufacturing I
Thursday, November 2, 2017 - 8:00am to 8:25am
In this work, we developed a statistical model to predict tablet dissolution profile in a continuous direct compaction manufacturing line. Tablets consisted of model API, Acetaminophen (APAP), lactose monohydrate as the filler, and magnesium stearate as lubricant. Multivariate effects were analyzed using Quality-by-Design methods. The experiment was based on a fractional factorial design with 30 experiments, including 3 repeated center points, to study the influence of four process variables â drug concentration (%), compaction force (KN), blending speed (rpm), and feed frame speed (rpm) â on the final product. Dissolution profiles of 180 tablets (six tablets for each experimental run) were obtained and fit into the Weibull model (including parameters of Î± and Î²), and the values of Î± and Î² were calculated. Multi variate analysis of variance (MANOVA) was used to determine the statistical differences between the dissolution profiles. The results indicated that compaction force and API concentration were the main parameters affecting tablet dissolution in this process. Therefore, a predictive model was developed to correlate the dissolution model parameters Î± and Î² to the process parameters. The model was verified using an independently manufactured validation set. The values of Î± and Î² of the validation set were estimated by the model. The dissolution profiles of these tablets were predicted using the estimated values of Î± and Î². The predicted dissolution profiles obtained from the model were in agreement with the experimental results using the similarity factor f2 value greater than 50. This work establishes an approach to the real time release testing (RTRt) of pharmaceutical tablets and the possibility of assessing the quality characteristics of tablets non-destructively.