Pharmaceutical dosage forms and drug delivery PDF
Preview Pharmaceutical dosage forms and drug delivery
Pharmacology and Toxicology N M a a Pharmaceutical Dosage Forms ra h n a t g o and Drug Delivery Second Edition Completely revised and updated, this second edition of Pharmaceutical Dosage Forms and Drug Delivery elucidates the basic principles of PPhhaarrmmaacceeuuttiiccaall pharmaceutics, dosage form design, and drug delivery. The authors integrate aspects of physical pharmacy, biopharmaceuticals, drug delivery, and biotechnology. The book highlights the increased attention that the recent spectacular advances in dosage form design and drug DDoossaaggee FFoorrmmss delivery, gene therapy, and nanotechnology have brought to the field. See what’s new in the Second Edition: S E • Additional author Ajit S. Narang brings an industrial practitioner C aanndd perspective with increased focus on pharmacy math and statistics, O and powders and granules N • Reorganized into the following three parts: Introduction, D Physicochemical Principles, and Dosage Forms • Chapters on pharmaceutical calculations, compounding principles, E DDrruugg DDeelliivveerryy D and powders and granules provide a complete spectrum of I application of pharmaceutical principles T • Expansion of review questions and answers clarifies concepts for I O students and adds to their grasp of key concepts covered in N the chapter SECOND EDITION • Coverage of complexation and protein binding aspects of physical pharmacy includes the basic concepts as well as recent progress in the field Although there are numerous books on the science of pharmaceutics and dosage form design, most cover different areas of the discipline Ram I. Mahato and do not provide an integrated approach to the topics. The integrated approach of this book not only provides a singular perspective of the Ajit S. Narang overall field, but it supplies a unified source of information for students, instructors, and professionals, saving them time and money. K12224 ISBN: 978-1-4398-4918-7 6000 Broken Sound Parkway, NW Suite 300, Boca Raton, FL 33487 90000 711 Third Avenue New York, NY 10017 2 Park Square, Milton Park Abingdon, Oxon OX14 4RN, UK 9 781439 849187 www.crcpress.com Pharmaceutical Dosage Forms and Drug Delivery SECOND E DITION Pharmaceutical Dosage Forms and Drug Delivery, Second Edition Ram I. Mahato and Ajit S. Narang Pharmacy : What It Is and How It Works, Third Edition William N. Kelly Essentials of Law and Ethics for Pharmacy Technicians, Third Edition Kenneth M. Strandberg Essentials of Human Physiology for Pharmacy, Second Edition Laurie Kelly McCorry Basic Pharmacokinetics Mohsen A. Hedaya Basic Pharmacology: Understanding Drug Actions and Reactions Maria A. Hernandez and Appu Rathinavelu Managing Pharmacy Practice: Principles, Strategies, and Systems Andrew M. Peterson Essential Math and Calculations for Pharmacy Technicians Indra K. Reddy and Mansoor A. Khan Pharmacoethics: A Problem-Based Approach David A. Gettman and Dean Arneson Pharmaceutical Care: Insights from Community Pharmacists William N. Tindall and Marsha K. Millonig Essentials of Pathophysiology for Pharmacy Martin M. Zdanowicz Quick Reference to Cardiovascular Pharmacotherapy Judy W. M. Cheng Essentials of Pharmacy Law Douglas J. Pisano Pharmacokinetic Principles of Dosing Adjustments: Understanding the Basics Ronald D. Schoenwald Pharmaceutical and Clinical Calculations, Second Edition Mansoor A. Khan and Indra K. Reddy Strauss’s Federal Drug Laws and Examination Review, Fifth Edition Revised Steven Strauss Inside Pharmacy: Anatomy of a Profession Raymond A. Gosselin and Jack Robbins Understanding Medical Terms: A Guide for Pharmacy Practice, Second Edition Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, and Steven Strauss Pharmaceutical Dosage Forms and Drug Delivery SECOND E DITION Ram I. Mahato Ajit S. Narang Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2012 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20110831 International Standard Book Number-13: 978-1 -4398-4919-4 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit- ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright. com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com I dedicate this book to my wife, Subhashini, and my children, Kalika and Vivek, for their love and support; my mother, Sarswati, for believing in me; and my students and mentors who have always helped me in my quest for learning and achieving higher goals. Ram I. Mahato I dedicate this book to the sacrifices of my parents, Tirath Singh and Gurdip Kaur, and my wife, Swayamjot; to the love of my brother, Supreet, and sons, Manvir and Arjun; and to the encouragement and confidence bestowed on me by my teachers and mentors that has always inspired me to be and do the very best. Ajit S. Narang Contents List of Figures ........................................................................................................xxv List of Tables .........................................................................................................xxxi Foreword ............................................................................................................xxxiii Preface..................................................................................................................xxxv Acknowledgments ..............................................................................................xxxvii Authors ................................................................................................................xxxix Part I Introduction Chapter 1 Drug Development and Regulatory Process ........................................3 Learning Objectives ..............................................................................3 1.1 Introduction ...............................................................................3 1.2 Identification of New Therapeutic Moieties ..............................5 1.2.1 Plant Sources ................................................................6 1.2.2 Organic Synthesis .........................................................6 1.2.3 Use of Animals .............................................................6 1.2.4 Genetic Engineering .....................................................6 1.2.5 Gene Therapy ...............................................................7 1.3 Preclinical Development............................................................7 1.4 Clinical Develo pment ................................................................8 1.4.1 Phase I Clinical Trials ..................................................8 1.4.2 Phase II Clinical Trials .................................................8 1.4.3 Phase III Clinical Trials ...............................................9 1.5 Formulation Development .........................................................9 1.6 Regulatory Interface ................................................................10 1.6.1 Investigational New Drug Application .......................10 1.6.2 New Drug Application ...............................................11 1.6.3 Approval and Post-Marketing Surveillance ...............11 1.6.4 Abbreviated New Drug Application ...........................12 1.6.5 Accelerated Development/Review .............................12 1.6.6 Role of FDA’s Advisory Committees .........................12 Review Questions ...............................................................................13 Further Reading .................................................................................13 Chapter 2 Pharmaceutical Considerations ..........................................................15 Learning Objectives ............................................................................15 2.1 Introduction .............................................................................15 2.2 Advantages of Pharmaceutical Dosage Forms ........................15 ix x Contents 2.3 Influential Factors in Dosage Form Design .............................16 2.3.1 Molecular Size and Volume .......................................17 2.3.2 Drug Solubility and pH ..............................................18 2.3.3 Lipophilicity and Partition Coefficient ......................20 2.3.4 Polymorphism ............................................................21 2.3.5 Stability ......................................................................23 2.3.6 pK /Dissociation Constants ........................................24 a 2.3.7 Degree of Ionization and pH-Partition Theory ..........28 2.3.7.1 Limitations of pH-Partition Theory ............28 Review Questions ...............................................................................29 Further Reading .................................................................................30 Chapter 3 Biopharmaceutical Considerations .....................................................33 Learning Objectives ............................................................................33 3.1 Introduction .............................................................................33 3.2 Diffusion ..................................................................................34 3.2.1 Drug Transport across a Polymeric Barrier ...............34 3.2.1.1 Molecular Diffusion ...................................34 3.2.1.2 Pore Diffusion .............................................35 3.2.1.3 Matrix Erosion ............................................35 3.2.2 Principles of Diffusion ...............................................35 3.2.2.1 Fick’s First Law ..........................................35 3.2.2.2 Fick’s Second Law ......................................36 3.2.3 Diffusion Rate ............................................................37 3.2.3.1 Diffusion Cell .............................................37 3.2.3.2 Spherical Membrane–Controlled Drug Delivery System ..........................................39 3.2.3.3 Pore Diffusion .............................................39 3.2.3.4 Determining Permeability Coefficient .......40 3.2.3.5 Lag Time in Nonsteady State Diffusion .....40 3.2.3.6 Matrix (Monolithic)-Type Nondegradable System ...............................41 3.2.3.7 Calculation Examples .................................41 3.3 Dissolution ...............................................................................42 3.3.1 Noyes–Whitney Equation ...........................................43 3.3.1.1 Calculation Example ...................................43 3.3.2 Factors Influencing Dissolution Rate .........................44 3.4 Absorption ...............................................................................46 3.4.1 Passive Transport ........................................................48 3.4.1.1 Simple Diffusion .........................................48 3.4.1.2 Carrier-Mediated Transport ........................48 3.4.1.3 Channel-Mediated Transport ......................48 3.4.2 Fick’s Laws of Diffusion in Drug Absorption ............49 3.4.3 Active Transport .........................................................50 Contents xi Review Questions ...............................................................................50 Further Reading ................................................................................52 Chapter 4 Pharmacy Math and Statistics ............................................................53 Learning Objectives ............................................................................53 4.1 Introduction .............................................................................53 4.2 Systems of Measure .................................................................53 4.2.1 Volume and Weight Interconversions .........................54 4.2.2 Temperature Interconversions ....................................55 4.2.3 Accuracy, Precision, and Significant Figures .............55 4.3 Ratio and Proportion ...............................................................56 4.4 Concentration Calculations .....................................................57 4.4.1 Percentage Solutions...................................................57 4.4.2 Concentrations Based on Moles and Equivalents ......57 4.4.3 Parts per Unit Concentrations ....................................58 4.4.4 Dilution of Stock Solutions ........................................59 4.4.5 Mixing Solutions of Different Concentrations ...........60 4.4.5.1 Alligation Medial ........................................60 4.4.5.2 Alligation Alternate ....................................60 4.4.6 Tonicity, Osmolarity, and Preparation of Isotonic Solutions .......................................................63 4.5 Clinical Dose Calculations ......................................................66 4.5.1 Dosage Adjustment Based on Body Weight or Surface Area ...............................................................67 4.5.2 Calculation of Children’s Dose ..................................67 4.5.3 Dose Adjustment for Toxic Compounds ....................69 4.5.4 Dose Adjustment Based on Creatinine Clearance .....71 4.6 Statistical Measures .................................................................73 4.6.1 Measures of Central Tendency ...................................73 4.6.2 Measures of Dispersion ..............................................74 4.6.3 Sample Probability Distributions ...............................75 4.6.3.1 Normal Distribution ....................................76 4.6.3.2 Log-Normal Distribution ............................76 4.6.3.3 Binomial Distribution .................................76 4.6.3.4 Poisson Distribution ....................................76 4.6.3.5 Student’s t-Distribution ...............................76 4.6.3.6 Chi-Square Distribution..............................78 4.7 Tests of Statistical Significance ...............................................78 4.7.1 Parametric and Nonparametric Tests .........................79 4.7.2 Null and Alternate Hypothesis ...................................80 4.7.3 Steps of Hypothesis Testing .......................................80 4.7.4 One-Tailed and Two-Tailed Hypothesis Tests ............81 4.7.5 Regions of Acceptance and Rejection ........................81 4.7.6 Probability Value and Power of a Test .......................82
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