Statistical thinking and knowledge management for quality-driven design and manufacturing in pharmaceuticals

The purpose of this article is to present the evolution of quality principles and how they have been implemented in the pharmaceutical industry. The article discusses the challenges that the FDA PAT Guidance and the ICH Q8, Q9 and Q10 Guidelines present to industry and provides a comprehensive overview of the basic tools that can be used to effectively build quality into products. The principles of the design of experiments, the main tools for statistical process analysis and control, and the requisite culture change necessary to facilitate statistical, knowledge-based management are also addressed. © 2010 Springer Science+Business Media, LLC

Response surface methodology for optimization and characterization of limonene-based coenzyme Q10 self-nanoemulsified capsule dosage form

The aim of this study was to systematically obtain a model of factors that would yield an optimized self-nanoemulsified capsule dosage form (SNCDF) of a highly lipophilic model compound, Coenzyme Q10 (CoQ). Independent variables such as amount of R-(+)-limonene (X1), surfactant (X2), and cosurfactant (X3), were optimized using a 3-factor, 3-level Box-Behnken statistical design. The dependent variables selected were cumulative percentage of drug released after 5 minutes (Y1) with constraints on drug release in 15 minutes (Y2), turbidity (Y3), particle size (Y4), and zeta potential (Y5). A mathematical relationship obtained,Y1=78.503+6.058X1 +13.738X2+5.986X3−25.831X12+9.12X1X2−26.03X1X3−38.67X22 +11.02X2X3−15.55X33 (r2=0.97), explained the main and quadratic effects, and the interaction of factors that affected the drug release. Response surface methodology (RSM) predicted the levels of factorsX1,X2, andX3 (0.0344, 0.216, and 0.240, respectively), for a maximized response ofY1 with constraints of >90% release onY2. The observed and predicted values ofY1 were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to obtain SNCDF with rapid (>90%) drug release within 5 minutes with desirable properties of low turbidity and particle size