A Novel Bending Point Criterion for Dissolution Profile Interpretation

Abstract

A novel bending point criterion was developed and compared with a number of existing criteria for the interpretation of certain dissolution profiles; these comparison criteria were the percentage dissolved at a fixed time point, the fitted Weibull parameters, and the area under the dissolution curve (AUC). The statistical bending point model was applied to dissolution curves that showed linear dissolution. The bending point model is based on a general linear model, and its confidence information is obtained using the variance-covariance matrix of the parameter estimates. Practically, three time points in the linear part and two time points on the plateau level are used for a reliable bending point estimation. A comparative study with three batches and three storage conditions of slow-release mucoadhesive buccal tablets was performed. The relative standard deviation (RSD) values of the bending point were typically between 1% and 5%, which are considerably lower than the corresponding values of the other criteria (typically between 3% and 15%). The bending point criterion is considered robust and stable for the characterization of certain dissolution profiles. Moreover, the bending point has a particular physical interpretation that is helpful in the framework of the slow-release application of this buccal tablet.

Key Words:

• Buccal tablet
• Dissolution
• Model-dependent analysis
• Statistics