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

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 d...

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Autores principales: Herneisey, Michele, Lambert, Eric, Kachel, Allison, Shychuck, Emma, Drennen, James K., Janjic, Jelena M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600169/
https://www.ncbi.nlm.nih.gov/pubmed/31151246
http://dx.doi.org/10.3390/molecules24112066
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author Herneisey, Michele
Lambert, Eric
Kachel, Allison
Shychuck, Emma
Drennen, James K.
Janjic, Jelena M.
author_facet Herneisey, Michele
Lambert, Eric
Kachel, Allison
Shychuck, Emma
Drennen, James K.
Janjic, Jelena M.
author_sort Herneisey, Michele
collection PubMed
description 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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spelling pubmed-66001692019-07-16 Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up Herneisey, Michele Lambert, Eric Kachel, Allison Shychuck, Emma Drennen, James K. Janjic, Jelena M. Molecules Article 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. MDPI 2019-05-30 /pmc/articles/PMC6600169/ /pubmed/31151246 http://dx.doi.org/10.3390/molecules24112066 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herneisey, Michele
Lambert, Eric
Kachel, Allison
Shychuck, Emma
Drennen, James K.
Janjic, Jelena M.
Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title_full Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title_fullStr Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title_full_unstemmed Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title_short Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up
title_sort quality by design approach using multiple linear and logistic regression modeling enables microemulsion scale up
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600169/
https://www.ncbi.nlm.nih.gov/pubmed/31151246
http://dx.doi.org/10.3390/molecules24112066
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