Prediction Factors for Quality Risks in the Pharmaceutical Development of Tablets Bisoprolol Fumarate with Indapamide.

Abstract

Background: An important characteristic of the quality-by-design approach is defining risk, which is a combination of the probability of harm and its severity. During risk assessment, it is essential to determine how the formulation, properties of active ingredients and excipients, and process parameters can potentially affect critical quality attributes or critical process parameters.

Objective: to develop an algorithm and a mathematical model for predicting quality risks in the pharmaceutical development of bisoprolol fumarate tablets with indapamide.

Methods: The software programs "Microsoft Excel 2016" and "Statistica 10.0" (StatSoft, Inc.) were used to predict potential risks and to build a regression model of quality-related risks for bisoprolol fumarate tablets with indapamide.

Results: A mathematical model for predicting the tablet quality risk has been developed, incorporating significant predictors: Carr's index for powder mixtures (Х1), evaluation of the pressing process (Х2), uniformity of tablet weight (Х3), tablets hardness testing (Х4), disintegration time (Х6). Four levels of quality risk are defined: low risk [0.8-1.0], moderate risk [0.6-0.8], high risk [0.4-0.6], and critical risk [0-0.4]. The calculated coefficient of determination of the forecasting model (R2=0.8168) testifies to its high quality.

Conclusion: The developed algorithm and mathematical model for predicting tablet quality risks, proposed for the first time, are highly informative and qualitative. It makes it possible to assess and predict risks related to the quality of tablets, arising from the influence of multiple factors.