PHARMACEUTICAL PRINCIPLES OF SOLID DOSAGE FORMS

Transcription

1 PHARMACEUTICAL PRINCIPLES OF SOLID DOSAGE FORMS J. T. Carstensen, Ph.D. Professor of Pharmacy University of Wisconsin Madison, Wisconsin TECHNOMIC ^PUBLISHING CO.. INC J 1.ANCASTER BASET,

2 TABLE OF CONTENTS Acknowledgements Introduction xv xiii Chapter 1. Absorption Attributes of a Dosage Form Pharmacokinetics. Absorption of the Drug Substance Oral Absorption. Fraction Absorbed Formulation Efficiency In vitro to in vivo Correlation The Intrinsic Dissolution Rate Constant Dissolution Testing Abbreviated New Drug Applications and Biobatches References Problems (Chapter 1) 13 Chapter 2. Powder Dosage Forms, Densities and Blending Drug Substance Per Se Powders Non-Cohesive Blending (Mixing) Preblending Segregation Cohesion and Friction Cohesive Blending. Ordered Mixing References Problems (Chapter 2) 31 vii

3 viii Chapter 3. Hard Shell Capsules and Apparent Densities Hard Shell Capsule Machines Factors Other Than Flow Affecting the Fill Apparent Density and Particle Sizes Factors Affecting Machine Operation Soft Shell Capsules Dissolution of Capsules References Problems (Chapter 3) 43 Chapter 4. Milling (Comminution) Ball Milling Hammer Mills Particle Sizes from Hammer Milling Attrition Mills Particle Shape and Size Definitions Normal Distributions References Problems (Chapter 4) 61 Chapter 5. Tablets Pills Single Punch Tablet Machines (Eccentric Machines) Bond Formation in Tablets Compression Profiles Thickness (Porosity) of a Tablet Hardness of Tablets Classification of Materials Regarding Compression Properties Direct Compression Size and Identification of Tablets Powder Flow Requirements for Tablet Granulations Powder Row Work and Energy Relations in Tablet Formation Disintegration of Tablets Tablet Dissolution Uncoated Tablet Ingredients References Problems (Chapter 5) 91 Chapter 6. Granulation and Drying The Wet Granulation Process 95

4 ix 6.2 Drying of Granulations References Problems (Chapter 6) 104 Chapter 7. Stability of Solid Dosage Forms Stability of Solid in the Presence of Moisture Statistics of the Straight Line (Linear Regression) Confidence Limits about Extrapolated Points Expiration Dating Slope Method for Determining Expiration Dates Accelerated Testing References Problems (Chapter 7) 128 Chapter 8. Crystalline Solids Morphological Considerations Drug Purification Crystal Systems Crystal Habit Vapor Pressure of Solids Solubility Measurements Polymorphism Metastable Solutions Effect on Biopharmaceutics References Problems (Chapter 8) 148 Chapter 9. DSC and Amorphates Differential Scanning Calorimetry (DSC) Amorphates Solubility and Amorphates Amorphous Sucrose Dosage Forms Stability of Amorphous Substances Polymers References Problems (Chapter 9) 157 Chapter 10. Hygroscopic Potential of Solids Water's Vapor Pressure Physically Moisture Sensitive Drugs Relative Humidity Vapor Pressures over Ideal Solutions 163

5 x 10.5 Vapor Pressure over Salt Solutions and Suspensions Water Vapor Pressure over Amorphous Substances Controlled Relative Humidity References Problems (Chapter 10) 168 Chapter 11. Pharmaceutical Packaging The Pharmaceutical Container-Closure System Measurement of Moisture Permeation Effect of Relative Humidity of the Environment Effect of Thickness of the Bottle The General Diffusion Equation Effect of Bottle Size USP Container Permeation Test Stability and Packaging References Problems (Chapter 11) 182 Chapter 12. Equilibrium Moisture Content of Solids 1& Hygroscopicity Equilibrium Moisture Curves for Salt-Hydrates Equilibrium Moisture Contents for Macromolecules Adsorption Isotherms of Silica Use of Desiccants in Packages References Problems (Chapter 12) 197 Chapter 13. Binary Phase Diagrams 1" 13.1 Physical Incompatibilities The Weight Arm Rule Impurity Determination Compound Separation in Tablets Molecular Compounds Lyophilization References Problems (Chapter 13) 209 Chapter 14. Micromeritics I m portance of Su rface Areas Surface Areas 211

6 xi 14.3 BET Isotherms Permeametry Particle Size Distribution Microscopy Surface Volume Mean Diameter Sieving Average Particle Size by Sieving Surface Area by Sieving Particle Size Distri butions i n Sievi ng References Problems (Chapter 14) 223 Chapter 15. Sustained Release Principles Bioadhesion Erosion Tablets Coated Beadlets Insoluble Matrix Osmotic Pump Hydrogels Microspheres References Problems (Chapter 15) 233 Answers to Problems 235 Author Index 249 Subject Index 253