How to Develop Robust Solid Oral Dosage Forms: From Conception to Post-Approval

Front Cover -- How to Develop Robust Solid Oral Dosage Forms -- How to Develop Robust Solid Oral Dosage Forms: From Conception to Post-Approval -- Copyright -- Contents -- Author Biography -- Foreword -- Preface -- Acknowledgments -- About the Expertise in Pharmaceutical Process Technology Series -- FORMAT -- SUBJECT MATTER -- TARGET AUDIENCE -- List of Abbreviations and Acronyms -- 1 - Rules of Drug Product Development -- 1.1 INTRODUCTION -- 1.2 THE BIG PICTURE -- 1.3 RULE 1: BIOPHARMACEUTICS AND BIOAVAILABILITY -- 1.4 RULE 2: MANUFACTURABILITY -- 1.5 RULE 3: STABILITY

1.6 RULE 4: BUSINESS ACUITY -- 1.7 BRING IT TOGETHER -- 1.7.1 Understanding the Regulatory Landscape -- 1.7.2 Understanding and Cultivating Partnerships -- 1.7.3 Understanding Time Lines -- 1.7.4 Anticipating Uncertainties -- 1.8 CLOSING THOUGHTS-DEVELOPING A PROBLEM-SOLVING ATTITUDE -- REFERENCES -- 2 - Pharmacokinetics and Preformulation -- 2.1 BIOPHARMACEUTICS AND PHARMACOKINETICS -- 2.1.1 Key Concepts -- 2.1.2 Assessment of Bioavailability -- 2.1.3 First-pass Effect and Relative Bioavailability -- 2.2 DRUG TRANSPORT IN SOLID ORAL DOSAGES -- 2.2.1 Passive Diffusion

2.2.2 The pH-Partition Hypothesis -- 2.2.3 Mechanisms of Drug Absorption-From Ingestion to Systemic Circulation -- 2.2.4 Factors Influencing Bioavailability -- 2.3 PROPERTIES IMPACTING DRUG DISSOLUTION -- 2.3.1 The Noyes-Whitney Equation -- 2.3.2 Diffusion Coefficient and Intrinsic Dissolution Rate Constant -- 2.3.3 Solubility -- 2.3.4 pKa and Henderson-Hasselbalch Equation -- 2.3.5 Particle Size and Distribution -- 2.4 PROPERTIES IMPACTING PERMEABILITY -- 2.5 PROPERTIES IMPACTING MANUFACTURABILITY -- 2.5.1 Polymorphism -- 2.5.2 Thermal Properties -- 2.5.3 Hygroscopicity

2.5.4 Organoleptic Properties -- 2.5.5 Bulk Powder Properties-Size, Density, and Flowability -- 2.5.6 Mechanical Properties and Compactability -- 2.6 CLOSING STATEMENTS-INITIATING NONCLINICAL STUDIES -- 2.6.1 Nonclinical Studies -- 2.6.2 Estimation of Initial Safe Starting Dose -- REFERENCES -- 3 - Formulation Development -- 3.1 QUALITY BY DESIGN AND RATIONAL DEVELOPMENT APPROACH -- 3.1.1 The Biopharmaceutical Classification System (BCS) -- 3.1.2 Impact of BCS on Dosage Form Design -- 3.1.3 Target Product Profile -- 3.1.4 Components of a Target Product Profile

3.2 QUALITY TARGET PRODUCT PROFILE -- 3.2.1 Type of Dosage Forms -- 3.2.2 Dose Strength -- 3.2.3 Dosage Form Size and Shape Selection -- 3.2.4 Palatability -- 3.2.5 Choice of Excipients -- 3.2.6 Container Closure System -- 3.3 DEVELOPING THE COMPOSITION -- 3.3.1 Drug-Excipient Compatibility Studies -- 3.3.2 Manufacturability -- 3.3.3 Most Commonly Used Manufacturing Processes for Solid Oral Dosages -- 3.3.4 Impact of Manufacturing Process on Excipient Selection -- 3.3.5 Understanding the Impact of Drug Loading -- 3.4 PUTTING IT ALL TOGETHER

3.4.1 Case Study I-Development of a Tablet Formulation and Preliminary Process

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