Molecules (May 2019)

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

  • Michele Herneisey,
  • Eric Lambert,
  • Allison Kachel,
  • Emma Shychuck,
  • James K. Drennen,
  • Jelena M. Janjic

DOI
https://doi.org/10.3390/molecules24112066
Journal volume & issue
Vol. 24, no. 11
p. 2066

Abstract

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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.

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