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“Development of Fixed Dose Combination Products” Workshop Report: Considerations of Gastrointestinal Physiology and Overall Development Strategy

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Abstract

The gastrointestinal (GI) tract is one of the most popular and used routes of drug product administration due to the convenience for better patient compliance and reduced costs to the patient compared to other routes. However, its complex nature poses a great challenge for formulation scientists when developing more complex dosage forms such as those combining two or more drugs. Fixed dose combination (FDC) products are two or more single active ingredients combined in a single dosage form. This formulation strategy represents a novel formulation which is as safe and effective compared to every mono-product separately. A complex drug product, to be dosed through a complex route, requires judicious considerations for formulation development. Additionally, it represents a challenge from a regulatory perspective at the time of demonstrating bioequivalence (BE) for generic versions of such drug products. This report gives the reader a summary of a 2-day short course that took place on the third and fourth of November at the Annual Association of Pharmaceutical Scientists (AAPS) meeting in 2018 at Washington, D.C. This manuscript will offer a comprehensive view of the most influential aspects of the GI physiology on the absorption of drugs and current techniques to help understand the fate of orally ingested drug products in the complex environment represented by the GI tract. Through case studies on FDC product development and regulatory issues, this manuscript will provide a great opportunity for readers to explore avenues for successfully developing FDC products and their generic versions.

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Funding

The authors received financial support from the Flemish Research Council (FWO – applicant number: 12R2119N).

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Authors and Affiliations

  1. Department of Pharmaceutical & Pharmacological Sciences, KU Leuven, Herestraat 49, Gasthuisberg, Box 921, 3000, Leuven, Belgium

    Bart Hens

  2. NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK

    Maura Corsetti

  3. Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK

    Maura Corsetti

  4. Department Engineering Pharmacy Section, Miguel Hernandez University, San Juan de Alicante, 03550, Alicante, Spain

    Marival Bermejo

  5. Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada

    Raimar Löbenberg

  6. Departamento de Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Av Vicuña Mackenna, 4860, Santiago, Chile

    Pablo M. González

  7. Clinical Development, Sandoz, Inc. (A Novartis Division), Princeton, New Jersey, 08540, USA

    Amitava Mitra

  8. Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey, 08903-0191, USA

    Divyakant Desai

  9. Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDASilver Spring, US Food & Drug Administration (US FDA), Prince Georges Counties, Maryland, USA

    Dakshina Murthy Chilukuri

  10. Subdepto. Biofarmacia y Equivalencia Terapéutica, Agencia Nacional de Medicamentos (ANAMED), Instituto de Salud Pública de Chile, Santiago, Chile y Facultad de Farmacia, Universidad de Valparaíso, Valparaíso, Chile

    Alexis Aceituno

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Correspondence to Bart Hens.

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Hens, B., Corsetti, M., Bermejo, M. et al. “Development of Fixed Dose Combination Products” Workshop Report: Considerations of Gastrointestinal Physiology and Overall Development Strategy. AAPS J 21, 75 (2019). https://doi.org/10.1208/s12248-019-0346-6

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  • DOI: https://doi.org/10.1208/s12248-019-0346-6

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