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Journal of Pharmaceutical Innovation

, Volume 7, Issue 3–4, pp 119–126 | Cite as

Adaptive Design Space as an Integrated Component of Quality by Design

  • Benoît Igne
  • Zhenqi Shi
  • Sameer Talwar
  • James K. DrennenIII
  • Carl A. AndersonEmail author
Research Article

Abstract

Introduction

The US Food and Drug Administration requires pharmaceutical companies to develop extensive process understanding prior to routine manufacturing of drug products. Through development and validation, drug manufacturers enhance their process understanding and identify an acceptable range of process parameters for each unit operation; this is referred to as the design space. Typically, limited work is done to study the effect of long-term raw material variations on the robustness of the design space. In the present study, the development of a design space for a tablet formulation containing two APIs (acetaminophen, caffeine) through a direct compression process was investigated.

Material and Methods

A design of experiment including different excipient ratios of microcrystalline cellulose and lactose, two croscarmellose sodium levels, four tablet compression forces, and four blend parameters was created using an industrial-size press to define a knowledge space. Quality attributes (disintegration time, dissolution, radial tensile strength, and friability) were measured and a design space derived. In order to test the robustness of the design space, raw material properties, specifically particle size of acetaminophen and ratio of lactose anhydrous to monohydrate, were modified. Also, compression parameters were varied.

Results

Tablets were analyzed for relevant critical quality attributes (CQAs) to investigate how variability in raw materials can change the design space. The modification of the process parameters was used as a means of compensating for raw material variability to produce tablets that met CQA requirements. An adaptive design space approach based on the adaptation of critical process parameters is proposed to facilitate the creation of tablets meeting specifications despite variation in raw material properties.

Keywords

Quality by design Knowledge space Design space Adaptive design space Raw material variability 

Notes

Acknowledgments

Authors would like to acknowledge Dr. Michael Moore and Robert W. Bondi, Jr. for their help in operating the tablet press to create the tablets used in this article.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Benoît Igne
    • 1
  • Zhenqi Shi
    • 2
  • Sameer Talwar
    • 2
  • James K. DrennenIII
    • 1
    • 2
  • Carl A. Anderson
    • 1
    • 2
    Email author
  1. 1.School of PharmacyDuquesne University Duquesne Center for Pharmaceutical TechnologyPittsburghUSA
  2. 2.Graduate School of Pharmaceutical SciencesDuquesne UniversityPittsburghUSA

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