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Format: 1 online resource (1,176 pages) : , illustrations

Edition: Second edition.

Note: Front Cover -- Developing Solid Oral Dosage Forms -- Copyright Page -- Dedication -- Contents -- List of Contributors -- Foreword -- I. Theories and Techniques in the Characterization of Drug Substances and Excipients -- 1 Solubility of Pharmaceutical Solids -- 1.1 Introduction -- 1.1.1 Implication of solubility in dosage form development -- 1.1.2 Basic concepts of solubility and dissolution -- 1.1.2.1 Ionic interactions -- 1.1.2.2 van der Waals interactions -- 1.1.2.3 Dispersion interactions -- 1.1.2.4 Hydrogen bonding -- 1.2 Thermodynamics of Solutions -- 1.2.1 Volume of mixing -- 1.2.2 Enthalpy of mixing -- 1.2.3 Entropy of mixing -- 1.2.4 Free energy of mixing -- 1.3 Theoretical Estimation of Solubility -- 1.3.1 Ideal solutions -- 1.3.2 Effect of crystallinity -- 1.3.3 Nonideal solutions -- 1.3.4 Regular solution theory -- 1.3.5 Aqueous solution theory -- 1.3.6 General solubility equation -- 1.4 Solubilization of Drug Candidates -- 1.4.1 Solubility enhancement by pH control and salt formation -- 1.4.1.1 Theoretical expressions to describe pH-solubility profiles -- 1.4.2 Solubilization using complexation -- 1.4.2.1 AL-type phase diagrams -- 1.4.2.2 AP-type phase diagrams -- 1.4.2.3 BS-type phase diagrams -- 1.4.3 Solubilization by cosolvents -- 1.4.4 Solubilization by surfactants (micellar solubilization) -- 1.4.5 Solubilization by combination of approaches -- 1.4.5.1 Combined effect of ionization and cosolvency -- 1.4.5.2 Combined effect of ionization and micellization -- 1.4.5.3 Combined effect of ionization and complexation -- 1.4.5.4 Combined effect of cosolvency and complexation -- 1.4.5.5 Combined effect of complexation and micellar solubilization -- 1.5 Experimental Determination of Solubility -- 1.5.1 Stability of solute and solvent -- 1.5.2 Shakers and containers -- 1.5.3 Presence of excess undissolved solute. , 1.5.4 Determination of equilibrium -- 1.5.5 Phase separation -- 1.5.6 Determination of solute content in the dissolved phase -- 1.5.7 Experimental conditions -- References -- 2 Crystalline and Amorphous Solids -- 2.1 Introduction -- 2.2 Definitions and Categorization of Solids -- 2.3 Thermodynamics and Phase Diagrams -- 2.3.1 Polymorphs -- 2.3.1.1 Enantiotropy and monotropy -- 2.3.1.2 Methods of determining stability relationships between polymorphs -- 2.3.1.2.1 Quantitative methods -- 2.3.1.2.1.1 Using heat of fusion data -- 2.3.1.2.1.2 Using eutectic fusion data -- 2.3.1.2.1.3 Using solubility/intrinsic dissolution rate data -- 2.3.1.2.1.4 Using solubility/intrinsic dissolution rate and heat of solution data -- 2.3.1.2.2 Qualitative methods -- 2.3.1.2.2.1 Using the definition -- 2.3.1.2.2.2 Using the heat of fusion rule -- 2.3.1.2.2.3 Using the heat of transition rule -- 2.3.2 Solvates/Hydrates -- 2.3.2.1 Anhydrate/Hydrate equilibrium at constant temperature -- 2.3.2.2 Temperature dependence of anhydrate/hydrate equilibrium -- 2.3.3 Cocrystals -- 2.3.4 Amorphous solids -- 2.4 Pharmaceutical Relevance and Implications -- 2.4.1 Solubility -- 2.4.2 Dissolution rate and bioavailability -- 2.4.3 Hygroscopicity -- 2.4.4 Reactivity and chemical stability -- 2.4.4.1 Topochemical reactions -- 2.4.4.2 Nontopochemical reactions -- 2.4.5 Mechanical properties -- 2.5 Transformations Among Solids -- 2.5.1 Induced by heat -- 2.5.1.1 Polymorphic transitions -- 2.5.1.2 Dehydration/Desolvation -- 2.5.1.3 Cocrystal formation -- 2.5.2 Induced by vapor -- 2.5.3 Induced by solvents -- 2.5.4 Induced by mechanical stresses -- 2.6 Methods of Generating Solids -- 2.6.1 Through gas -- 2.6.2 Through liquid -- 2.6.2.1 Through neat liquid -- 2.6.2.2 Through solution -- 2.6.2.2.1 Solvent evaporation -- 2.6.2.2.2 Antisolvent addition -- 2.6.2.2.3 Reactive solvent addition. , 2.6.2.2.4 Temperature gradient -- 2.6.2.2.5 Suspension method -- 2.6.3 Through solid -- 2.7 Amorphous Drugs and Solid Dispersions -- 2.7.1 Characteristics of amorphous phases -- 2.7.1.1 Origin of the glass transition -- 2.7.1.2 Configurational thermodynamic quantities -- 2.7.1.3 Molecular relaxation in the amorphous state -- 2.7.2 Characteristics of amorphous solid dispersions -- 2.7.2.1 Thermodynamic analyses and phase miscibility -- 2.7.2.1.1 Entropy of mixing -- 2.7.2.1.2 Enthalpy of mixing -- 2.7.2.1.3 Free energy of mixing -- 2.7.2.2 Molecular mobility in amorphous solid dispersions -- 2.7.2.3 Solubility in polymeric matrix -- 2.7.3 Crystallization of amorphous drugs and dispersions -- 2.7.3.1 Molecular mobility -- 2.7.3.2 Free energy driving force -- 2.7.3.3 Configurational entropy -- 2.7.3.4 Crystallization inhibition -- 2.8 Special Topics -- 2.8.1 Polymorph screening and stable form screening -- 2.8.2 High-Throughput crystallization -- 2.8.3 Miniaturization in crystallization -- References -- 3 Solid-State Characterization and Techniques -- 3.1 Introduction -- 3.2 Microscopy -- 3.2.1 Optical microscopy -- 3.2.2 Electron microscopy -- 3.2.3 Probe microscopy -- 3.3 Powder X-ray Diffraction -- 3.4 Thermal Analysis -- 3.4.1 Differential scanning calorimetry -- 3.4.1.1 Instrumentation -- 3.4.1.2 Applications -- 3.4.1.2.1 Melting and phase diagram -- 3.4.1.2.2 Characterization of polymorphs -- 3.4.1.2.3 Characterization of hydrates -- 3.4.1.2.4 Characterization of amorphous phases -- 3.4.2 Thermogravimetric analysis -- 3.4.3 Microcalorimetry -- 3.5 Vibrational Spectroscopy -- 3.5.1 IR and Raman spectroscopy -- 3.5.1.1 IR spectroscopy -- 3.5.1.2 Raman spectroscopy -- 3.5.2 SSNMR spectroscopy -- 3.6 Moisture Sorption -- 3.7 Hyphenated Techniques -- 3.8 Conclusion -- References -- 4 API Solid-Form Screening and Selection -- 4.1 Introduction. , 4.2 Solid-Form Selection Considerations -- 4.2.1 Key physicochemical property considerations -- 4.2.1.1 Solid-form stability -- 4.2.1.2 Hygroscopicity -- 4.2.1.3 Solubility, dissolution rate, and bioavailability -- 4.2.2 Considerations for various forms -- 4.2.2.1 Salts -- 4.2.2.1.1 pH-solubility profile and salt solubility -- 4.2.2.1.2 Selection of counterions and salt formation -- 4.2.2.1.3 Dissolution and oral absorption of salts -- 4.2.2.1.4 Toxicity of counterions -- 4.2.2.1.5 Chemical stability considerations -- 4.2.2.1.6 Disproportionation of salts -- 4.2.2.1.7 Dosage form consideration -- 4.2.2.2 Cocrystals -- 4.2.2.2.1 Selection of coformer -- 4.2.2.3 Polymorphs, solvates, and hydrates -- 4.2.2.4 Amorphous forms -- 4.3 Screening SOLID-FORMS of API -- 4.3.1 Screening techniques -- 4.3.2 High-throughput screening -- 4.3.3 Manual screens -- 4.3.4 Alternate screens -- 4.4 Identification and Analysis of Forms -- 4.4.1 Single-crystal and PXRD -- 4.4.2 Thermal techniques -- 4.4.3 Spectroscopic techniques -- 4.5 Conclusions -- 4.6 Case Studies -- 4.6.1 Case study 1: RPR111423144 -- 4.6.2 Case study 2: LY333531145 -- 4.6.3 Case study 3 -- References -- 5 Drug Stability and Degradation Studies -- 5.1 Introduction -- 5.2 Chemical Stability -- 5.2.1 Solution kinetics -- 5.2.2 Rate equations -- 5.2.3 Elemental reactions and reaction mechanism -- 5.2.4 Typical simple order kinetics -- 5.2.4.1 Zero-order reactions -- 5.2.4.2 First-order reactions -- 5.2.4.3 Second-order reactions -- 5.2.4.4 Apparent pseudokinetic orders -- 5.2.5 Complex reactions -- 5.2.5.1 Reversible reactions -- 5.2.5.2 Parallel reactions -- 5.2.5.3 Consecutive reactions -- 5.2.6 Arrhenius equation, collision theory, and transition state theory -- 5.2.6.1 Arrhenius equation -- 5.2.6.2 Classic collision theory of reaction rates -- 5.2.6.3 Transition state theory. , 5.2.7 Catalysts and catalysis -- 5.2.7.1 Specific acid-base catalysis -- 5.2.7.2 General acid-base catalysis -- 5.2.8 pH-rate profiles -- 5.2.8.1 V-shaped, U-shaped, and other truncated pH-rate profiles -- 5.2.8.2 Sigmoidal pH-rate profiles -- 5.2.8.3 Bell-shaped pH-rate profiles -- 5.2.8.4 More complicated pH-rate profiles -- 5.2.9 Solid-state reaction kinetics -- 5.2.10 Solid-state kinetic models -- 5.2.10.1 Reactions involving nucleation -- 5.2.10.2 Avrami-Erofeev equation -- 5.2.10.3 Prout-Tompkins equation -- 5.2.10.4 Reactions controlled by diffusion -- 5.2.10.5 Reactions governed by phase boundaries -- 5.2.10.6 Higher (nth)-order reactions -- 5.2.10.7 Bawn kinetics -- 5.2.10.8 Model-fitting versus model-free approaches -- 5.2.11 Physical parameters affecting solid-state kinetics -- 5.2.12 The role of moisture -- 5.2.13 Topochemical reactions -- 5.3 Common Pathways of Drug Degradation -- 5.3.1 Hydrolysis -- 5.3.1.1 Hydrolysis of carboxylic acid derivatives -- 5.3.1.2 Hydrolysis of acetals and ketals -- 5.3.1.3 Hydrolysis of other carbonyl derivatives -- 5.3.1.4 Miscellaneous hydrolysis reactions -- 5.3.2 Oxidative degradation -- 5.3.2.1 Mechanisms of oxidation -- 5.3.2.2 Prediction of oxidative stability -- 5.3.2.3 Functional groups susceptible to oxidation -- 5.3.3 Photochemical degradation -- 5.3.3.1 Light -- 5.3.3.2 Light absorption, excitation, and photochemical reactions -- 5.3.3.3 Photooxidation -- 5.3.4 Other degradation pathways -- 5.4 Experimental Approaches to Studying the Chemical Degradation of Drugs -- 5.4.1 Solution thermal degradation studies -- 5.4.2 Solid-state thermal degradation studies -- 5.4.3 Oxidative degradation studies -- 5.4.4 Photodegradation studies -- 5.5 Physical Stability and Phase Transformations -- 5.5.1 Types of phase transformations -- 5.5.2 Mechanisms of phase transformations. , 5.5.2.1 Solid-state transitions.

Additional Edition: ISBN 0-12-802447-X

Additional Edition: ISBN 0-12-802637-5

Language: English