Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up

Molecules. 2019 May 30;24(11):2066. doi: 10.3390/molecules24112066.

Abstract

The development of pharmaceutical nanoformulations has accelerated over the past decade. However, the nano-sized drug carriers continue to meet substantial regulatory and clinical translation challenges. In order to address some of these key challenges in early development, we adopted a quality by design approach to develop robust predictive mathematical models for microemulsion formulation, manufacturing, and scale-up. The presented approach combined risk management, design of experiments, multiple linear regression (MLR), and logistic regression to identify a design space in which microemulsion colloidal properties were dependent solely upon microemulsion composition, thus facilitating scale-up operations. Developed MLR models predicted microemulsion diameter, polydispersity index (PDI), and diameter change over 30 days storage, while logistic regression models predicted the probability of a microemulsion passing quality control testing. A stable microemulsion formulation was identified and successfully scaled up tenfold to 1L without impacting droplet diameter, PDI, or stability.

Keywords: microemulsions; modeling; quality by design (QbD).

MeSH terms

  • Drug Compounding* / methods
  • Drug Stability
  • Emulsions*
  • Linear Models*
  • Logistic Models*

Substances

  • Emulsions