Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets
Open Access
- 23 July 2015
- journal article
- Published by Springer Science and Business Media LLC in AAPS PharmSciTech
- Vol. 17 (2), 233-244
- https://doi.org/10.1208/s12249-015-0349-2
Abstract
Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.Keywords
This publication has 27 references indexed in Scilit:
- Assessment of the critical factors affecting the porosity of roller compacted ribbons and the feasibility of using NIR chemical imaging to evaluate the porosity distributionInternational Journal of Pharmaceutics, 2011
- Use of Placket–Burman Statistical Design to Study Effect of Formulation Variables on the Release of Drug from Hot Melt Sustained Release ExtrudatesAAPS PharmSciTech, 2010
- A Bayesian Approach to the ICH Q8 Definition of Design SpaceJournal of Biopharmaceutical Statistics, 2008
- Response surface methodology for optimization and characterization of limonene-based coenzyme Q10 self-nanoemulsified capsule dosage formAAPS PharmSciTech, 2004
- Physical and Lubrication Properties of Magnesium StearateJournal of Pharmaceutical Sciences, 1992
- Effect of Mixing on the Lubrication of Crystalline Lactose by Magnesium StearateDrug Development and Industrial Pharmacy, 1980
- An Efficient Method of Estimating Seemingly Unrelated Regressions and Tests for Aggregation BiasJournal of the American Statistical Association, 1962
- Some New Three Level Designs for the Study of Quantitative VariablesTechnometrics, 1960
- A CONFIDENCE REGION FOR THE SOLUTION OF A SET OF SIMULTANEOUS EQUATIONS WITH AN APPLICATION TO EXPERIMENTAL DESIGNBiometrika, 1954
- THE DESIGN OF OPTIMUM MULTIFACTORIAL EXPERIMENTSBiometrika, 1946