M ETHODS IN P HARMACOLOGY

Transcription

1 M ETHODS IN P HARMACOLOGY AND T OXICOLOGY Series Editor Y. James Kang University of Louisville School of Medicine Prospect, Kentucky, USA For further volumes:

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3 Process Simulation and Data Modeling in Solid Oral Drug Development and Manufacture Edited by Marianthi G. Ierapetritou and Rohit Ramachandran Rutgers University, Piscataway, NJ, USA

4 Editors Marianthi G. Ierapetritou Rutgers University Piscataway, NJ, USA Rohit Ramachandran Rutgers University Piscataway, NJ, USA ISSN ISSN (electronic) Methods in Pharmacology and Toxicology ISBN ISBN (ebook) DOI / Library of Congress Control Number: Springer New York Heidelberg Dordrecht London # Springer Science+Business Media New York 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Humana Press is a brand of Springer Springer Science+Business Media LLC New York is part of Springer Science+Business Media (

5 Preface The need for a more structured approach to process and product development has been recently identified in the pharmaceutical industry in order to consistently guarantee quality and value to processes and products. This need has been formally identified by the pharmaceutical industry as the Quality by Design (QbD) initiative and has been in the center of attention over the last few years. To enable the implementation of this concept, there is a need for quantitative characterization of process and product performance. The goal of this handbook is to provide pharmaceutical engineers with an introduction to the current state of the art in modeling and simulation of pharmaceutical processes and to summarize a number of practical applications of such methodologies in drug product development. Chapters include reviews of the simulation and modeling methodologies, data collection and analysis, development of novel sensing techniques, development and integration of individual unit models, optimization approaches for data-based models, design space evaluation techniques, informatics-based methodologies, and emerging topics in pharmaceutical process development. The first chapter focuses on examples of more mechanistic models developed in pharmaceutical manufacturing and specifically addresses the modeling of fluid bed granulation, tablet coating, and spray drying. The importance of the integration of such models in existing manufacturing workstreams is highlighted. Chapter 2 provides a detailed review of Population Balance Models (PBM) as one of the most promising alternatives to represent particulate systems. The distributed nature of the PBM makes it an appropriate modeling framework for pharmaceutical powder-based drug manufacturing. Material properties and how they affect product and process performance are discussed in Chap. 3. In particular, specific properties of raw materials and the techniques used to measure them are described, and the state of the art of applying this information to define product formulation is also presented. Chapter 4 reviews one of the most commonly used mechanistic approaches to model particular systems, which is Discrete Element Method (DEM). The main advantage of this approach is that it can capture mechanistic, particle-scale information such as velocity and collision profiles. In pharmaceutical manufacturing, it is important to establish the right procedures to guarantee the consistency in process performance. Chapter 5 reviews the procedures used for the development of near infrared (NIR) spectroscopic methods and describes examples of the most recently developed approaches based on partial least squares (PLS) calibration methods that minimize the number of samples used. Following the ideas on latent-variable modeling techniques, Chap. 6 presents how those approaches can be used to support pharmaceutical development and manufacturing activities. Chapter 7 is dedicated to control strategies required to support the switch from batch to continuous models of operations for the production of pharmaceutical products. A general methodology required to design and implement a control system is presented together with the required software and hardware of the control platform. Chapters 8 and 9 focus on the importance of mathematical modeling for process simulation, optimization, and the development of the design space for pharmaceutical process operations. In particular, Chap. 8 reviews the approaches that are used to define process feasibility and how v

6 vi Preface those are applied for pharmaceutical manufacturing. Chapter 9 provides a review of the optimization methodologies that have been applied to achieve better performance in pharmaceutical manufacturing. Finally, Chapter 10 provides a very detailed step-by-step description of the manufacturing stages involved in the production of solid dosage forms. Process analytical technology (PAT) devoted to the continuous manufacturing of solidbased drugs is also described. It is hoped that the collection of these papers will promote research into the process systems methodologies and their application in pharmaceutical product and process development, which will undoubtedly become an increasingly important area in the future. Piscataway, NJ, USA Marianthi G. Ierapetritou Rohit Ramachandran

7 Contents Preface..... Contributors... 1 Applications of Modeling in Oral Solid Dosage Form Development and Manufacturing Olav Lyngberg, Lieve Bijnens, Jeroen Geens, Alex Marchut, Steve Mehrman, and Elisabeth Schafer 2 Population Balance Models for Pharmaceutical Processes Anwesha Chaudhury, Maitraye Sen, Dana Barrasso, and Rohit Ramachandran 3 A Quantitative Approach to Understand Raw Material Variability Sara Koynov and Fernando J. Muzzio 4 Discrete Element Modeling of Solid Dosage Manufacturing Processes Dana Barrasso and Rohit Ramachandran 5 A Procedure for Developing Quantitative Near Infrared (NIR) Methods for Pharmaceutical Products Rodolfo J. Romañach, Andrés D. Román-Ospino, and Manel Alcalà 6 Advanced Process Decision Making Using Multivariate Latent Variable Methods Matteo Ottavian, Emanuele Tomba, and Massimiliano Barolo 7 Advanced Control of Continuous Pharmaceutical Tablet Manufacturing Processes Ravendra Singh, Carlos Velazquez, Abhishek Sahay, Krizia M. Karry, Fernando J. Muzzio, Marianthi G. Ierapetritou, and Rohit Ramachandran 8 Mathematical Tools for the Quantitative Definition of a Design Space Amanda Rogers and Marianthi G. Ierapetritou 9 Optimization Methodologies for the Production of Pharmaceutical Products M. Sebastian Escotet-Espinoza, Amanda Rogers, and Marianthi G. Ierapetritou 10 An Overview of Pharmaceutical Manufacturing for Solid Dosage Forms Stephan Sacher and Johannes G. Khinast Index v ix vii

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9 Contributors MANEL ALCALÀ Grup de Quimiometría Aplicada, Departament de Química, Unitat de Química Analítica, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain MASSIMILIANO BAROLO Computer-Aided Process Engineering Laboratory (CAPE-Lab), Department of Industrial Engineering, University of Padova, Padova, PD, Italy DANA BARRASSO Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA LIEVE BIJNENS Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceuticals, Beerse, Belgium ANWESHA CHAUDHURY Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA M. SEBASTIAN ESCOTET-ESPINOZA Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA JEROEN GEENS Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceuticals, Beerse, Belgium MARIANTHI G. IERAPETRITOU Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA KRIZIA M. KARRY Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA JOHANNES G. KHINAST Research Center for Pharmaceutical Engineering (RCPE), Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria SARA KOYNOV Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA OLAV LYNGBERG Janssen Supply Chain, Technical Operations, Janssen Pharmaceuticals, Raritan, NJ, USA ALEX MARCHUT Janssen Supply Chain, Technical Operations, Janssen Pharmaceuticals, Raritan, NJ, USA STEVE MEHRMAN Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceuticals, Beerse, Belgium FERNANDO J. MUZZIO Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA MATTEO OTTAVIAN Manufacturing Science & Technology, Sandoz Industrial Products S.p.A., Rovereto, TN, Italy ROHIT RAMACHANDRAN Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA AMANDA ROGERS Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA ix

10 x Contributors ANDRÉS D. ROMÁN OSPINO Department of Chemistry, Recinto Universitario de Mayagüez, Mayagüez, PR, USA RODOLFO J. ROMAÑACH Department of Chemistry, Recinto Universitario de Mayagüez, Mayagüez, PR, USA STEPHAN SACHER Research Center for Pharmaceutical Engineering (RCPE), Graz, Austria ABHISHEK SAHAY Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA ELISABETH SCHAFER Janssen Supply Chain, Technical Operations, Janssen Pharmaceuticals, Raritan, NJ, USA MAITRAYE SEN Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA RAVENDRA SINGH Department of Chemical and Biochemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), Rutgers, The State University of New Jersey, Piscataway, NJ, USA EMANUELE TOMBA Technical Development Drug Product, GSK Vaccines, Siena, SI, Italy CARLOS VELAZQUEZ Department of Chemical Engineering, Engineering Research Center for Structured Organic Particulate Systems (ERC-SOPS), University of Puerto Rico Mayaguez, Mayaguez, PR, USA