Download Amorphous Solid Dispersions.pdf PDF

TitleAmorphous Solid Dispersions.pdf
File Size15.2 MB
Total Pages702
Table of Contents
About the Editors
Part I ASD Introduction
	Chapter 1 Fundamentals of Amorphous Systems: Thermodynamic Aspects
		1.1 Introduction
			1.1.1 Function of ``Dissolved Drugs'' in Absorption
		1.2 Structural Aspects
		1.3 Thermodynamic Aspects
			1.3.1 Two Approaches to Understanding Neat Amorphous Forms
			1.3.2 Description of Forming a Solution
			1.3.3 Calculating the Gibbs Energy Change GS of Forming a Solution
			1.3.4 Solubility and Chemical Potential
			1.3.5 Amorphous Versus Crystalline Form Solubility
		1.4 The Microscopic View
			1.4.1 Interaction Versus Total Energy
			1.4.2 Extension to Macroscopic Systems
		1.5 Glasses and Amorphous Forms
			1.5.1 Thermodynamic Implications of the Glass Transition
		1.6 Implications for Solubility and Dissolution
		1.7 Implications for Physical Stability
		1.8 Kinetic Considerations
		1.9 Summary and Closing Remarks
	Chapter 2 Theoretical Considerations in Developing Amorphous Solid Dispersions
		2.1 Introduction
		2.2 Classification of Solid Dispersions
			2.2.1 Eutectic Mixtures
			2.2.2 Solid Solutions
			2.2.3 Glass Solutions
			2.2.4 Glass Suspensions
		2.3 Theoretical Considerations Regarding Solid Dispersions
			2.3.1 Solubility Advantage of the Amorphous Form
			2.3.2 Glass-Forming Ability (GFA) and Glass Stability (GS)
			2.3.3 Calculation of Physical Stability Kohlrausch--Williams--Watts (KWW) Equation AG Equation Thermodynamic Properties
		2.4 Drug--Polymer Miscibility: Theoretical Approaches
			2.4.1 General Thermodynamics of Mixing
			2.4.2 Prediction of Drug--Polymer Miscibility Flory--Huggins (F--H) Lattice Theory Estimation of the Interaction Parameter by Solubility Parameter Approach Estimation of the Interaction Parameter Using Melting Point Depression In Silico Estimation of Miscibility
			2.4.3 Impact of Temperature, Pressure, and Moisture on Miscibility Impact of Temperature Impact of Moisture Impact of Pressure
		2.5 Drug (Crystalline) Solubility Within a Polymer Matrix
			2.5.1 Determination of Drug Solubility Within a Polymer Matrix Melting Point Depression Methods Recrystallization from Supersaturated Glass Solutions F--H Interaction Parameter Changes in Gibbs Energy Solubility Determination in PEG
			2.5.2 Summary of Solubility Determination Methods
			2.5.3 Effect of Drug Solubility on the Physical Stabilityof the Glass Solution
			2.5.4 Maintenance of Supersaturated Conditions: The ``Spring and Parachute Effect''
		2.6 Summary
	Chapter 3 Overview of Amorphous Solid Dispersion Technologies
		3.1 Introduction and Background
		3.2 Solvent Evaporation
			3.2.1 Solvent Selection
			3.2.2 Selection of Polymer and Other Additives
			3.2.3 Selection of Solvent Evaporation Process
		3.3 Hot-Melt Extrusion
			3.3.1 Selection of Polymer, Additives (Plasticizer, Flow Aid and Surfactant), and Drug Loading in HME
			3.3.2 Selection of Extruder and the Processing Conditions
			3.3.3 Downstream Processing and Performance Optimization
		3.4 Microprecipitation: MBP
			3.4.1 MBP Methodology
			3.4.2 Preparation of ASD
			3.4.3 Downstream Processing
		3.5 Supercritical Fluid Processing
		3.6 KinetiSol
		3.7 Ultrasonic-Assisted Compaction
		3.8 Cryogenic Processing
		3.9 Electrospinning and Rotating Jet Spinning
		3.10 Milling and Cryogrinding
		3.11 Hot-Melt Coating/Granulation
		3.12 Process Selection Guide
		3.13 Summary
	Chapter 4 Excipients for Amorphous Solid Dispersions
		4.1 Introduction
		4.2 Challenges of Amorphous Solid Dispersions
		4.3 Role of Excipients in Amorphous Solid Dispersions
			4.3.1 Glass Transition Temperature (Tg)
			4.3.2 Molecular Mobility
			4.3.3 Polymer Molecular Weight
			4.3.4 Drug--Polymer Ratio
			4.3.5 Solubility Parameters
			4.3.6 Solid Solution Capacity
			4.3.7 Solubilization Capacity
			4.3.8 Hygroscopicity
			4.3.9 Chemical Reactivity
		4.4 Classification of Excipients
			4.4.1 Nonionic/Non-pH-Dependent Polymers Polyvinyllactam Polymers Polyvinylpyrrolidone (Povidone) Copovidone (Kollidon® VA64/ PlasdoneTM S-630) Polyvinylcaprolactam--Polyvinyl Acetate--Polyethyelne Glycol Graft Copolymer (Soluplus®) Cellulose Ethers Hydroxypropyl Methyl Cellulose Hydroxypropyl Cellulose
			4.4.2 Ionic/pH-Dependent Polymers Cationic Polymers Eudragit® EPO Anionic Polymers Eudragit® L 100-55 Eudragit® L-100 Eudragit® S100 Hypromellose Acetate Succinate Hydroxypropyl Methylcellulose Phthalate Cellulose Acetate Phthalate Polyvinyl Acetate Phthalate
			4.4.3 Non-Polymeric Excipients Amino Acid Derivatives Mesoporous Silica Solubilizers and Wetting Agents Plasticizers Antioxidants
			4.4.4 Selection and Optimization of Excipients
		4.5 Impact of Excipients on Amorphous Solid Dispersion Processes
			4.5.1 Melting (Fusion) Methods
			4.5.2 Solvent-Based Methods
			4.5.3 Solvent-Controlled Precipitation/Microprecipitated Bulk Powder
		4.6 Marketed Products Using Amorphous Solid Dispersions
		4.7 Safety and Regulatory Consideration of Excipients
		4.8 Summary
Part II Technologies
	Chapter 5 Miniaturized Screening Tools for Polymer and Process Evaluation
		5.1 Introduction
		5.2 ASD Screening Assessment
			5.2.1 API Physicochemical Properties Evaluation for ASD Feasibility
			5.2.2 Drug--Polymer Interaction for ASD Feasibility Drug--Polymer Interactions in the Solid State Drug--polymer Interactions in Aqueous Media for ASD Feasibility
		5.3 ASD Miniaturized Screening
			5.3.1 Solvent-Casting Method 96-Well Plate Vacuum Dry System for ASD Screening SPADS Approach SPADS Dissolution Assay SPADS Interaction Assay SPADS Imaging Assay
			5.3.2 Solvent-Shift Method for the Selection of Polymers
			5.3.3 Coprecipitation Method
			5.3.4 Melt-fusion Method
			5.3.5 Freeze-Drying method
			5.3.6 Spin-coating Method
		5.4 Miniaturization Screening Strategy and Decision Making
			5.4.1 Polymer Evaluation in Miniaturized Screening
			5.4.2 Process Evaluation in Miniaturized Screening
		5.5 Summary
	Chapter 6 Hot-Melt Extrusion for Solid Dispersions: Composition and Design Considerations
		6.1 Introduction
		6.2 Enabled Technology Platform Selection
		6.3 Drug: Polymer Systems for Extrusion
			6.3.1 Classes I and II: Solid/Liquid Systems
			6.3.2 Class I: High TmeltAPI, Negligible Melting Point Depression, and Viscous Polymer System
			6.3.3 Class II: High TmeltAPI, Negligible Melting Point Depression, and Inviscid Polymer System
			6.3.4 Classes III and VI: Liquid/Liquid Systems
			6.3.5 Class III: High TmeltAPI, Significant Melting Point Depression, and Viscous Polymer System
			6.3.6 Class IV: High TmeltAPI, Significant Melting Point Depression, and Inviscid Polymer System
			6.3.7 Class V: Low TmeltAPI and Viscous Polymer System
			6.3.8 Class VI: Low TmeltAPI and Inviscid Polymer System
		6.4 Formulation Design
			6.4.1 Early Formulation Development Considerations
			6.4.2 Pilot-Scale Development Considerations
		6.5 Solid-State Characterization of Melt-Extruded Amorphous Dispersions
		6.6 Detection of Crystallization and Amorphous--Amorphous Phase Separation
		6.7 Mechanical Properties of Melt-Extruded Amorphous Dispersions
		6.8 Summary
	Chapter 7 HME for Solid Dispersions: Scale-Up and Late-Stage Development
		7.1 Introduction to Commercialization of Extruded Dispersions
		7.2 Integrating Melt Extrusion into Drug Substance Manufacturing
			7.2.1 HME Devolatilization
			7.2.2 Extrusion Process Parameters and Raw Material Properties for Devolatilization
			7.2.3 Extruder Design for Devolatilization
			7.2.4 Integrated Drug Substance and Drug Product Processing
		7.3 Scale-Up of Extrusion Operations
			7.3.1 Production Considerations at Different Scales
			7.3.2 Tools for Assessing Scale-Up
			7.3.3 Types of Scale-Up
			7.3.4 Scaling in Parallel
			7.3.5 Scaling with Time
			7.3.6 Scaling with Equipment Size
			7.3.7 Volumetric Scale-Up Strategy
			7.3.8 Heat Transfer Limited Scale-Up Strategy
		7.4 Process Analytical Technology for Melt Extrusion
			7.4.1 Process Understanding
			7.4.2 Process Fault Detection
			7.4.3 Real-Time Quality Assurance
			7.4.4 PAT Operationalization
		7.5 Quality by Design for Melt Extrusion
			7.5.1 Quality Target Product Profile, CQA definition, and Initial RA
			7.5.2 Late-Stage Risk Assessment and Control Strategy
			7.5.3 Product Lifecycle Management
		7.6 Summary
	Chapter 8 Spray Drying: Scale-Up and Manufacturing
		8.1 Technology Transfer and Scale-Up to Commercial Units
			8.1.1 Manufacturing Scales Lab to Production Equipment Considerations for the Selection of Scale
			8.1.2 Nozzle Selection Rotary Nozzles Two-Fluid Nozzles Pressure Nozzles Ultrasonic Nozzles Considerations for the Selection of Nozzle
			8.1.3 Typical Challenges Product Accumulation Improper Atomization Chemical Stability Degradation of the Feed Solution Degradation Inside the Spray Dryer Chamber
			8.1.4 Modeling Tools and Mechanistic Interpretation Thermodynamic Modeling Droplet Size Estimation Particle Formation
			8.1.5 Scale-Up Methodology Thermodynamic Step Atomization Step Particle Formation Step
			8.1.6 Process Intensification
			8.1.7 Conclusions
		8.2 Development of a Manufacturing Process of a Spray-Dried Dispersion Under a Quality by Design Approach
			8.2.1 Methodology Overview
			8.2.2 Case Study Overview
			8.2.3 Target Product Profile and Critical Quality Attributes
			8.2.4 Risk Assessment
			8.2.5 Process Modeling Screening Stage Optimization Stage Robustness Stage
			8.2.6 Design Space
			8.2.7 Mechanistic Understanding
		8.3 Conclusions
	Chapter 9 Design and Development of HPMCAS-Based Spray-Dried Dispersions
		9.1 Introduction
		9.2 Background: Efforts to Enhance the Solubilityof Pharmaceutical Compounds
		9.3 SDD Formulation Selection and Manufacture
		9.4 HPMCAS Attributes for Use in SDD Platform Technology
		9.5 Speciation of HPMCAS-Based SDDs
			9.5.1 Nanoparticle Formation Mechanism
			9.5.2 Erosion Dissolution Mechanism
			9.5.3 Dissolution Species
		9.6 Testing Methods
			9.6.1 Centrifugal Dissolution Tests
			9.6.2 Membrane Permeation Test
		9.7 Performance of the SDD Platform
			9.7.1 SDD Performance In Vivo
			9.7.2 Stability
		9.8 Conclusions
	Chapter 10 MBP Technology: Composition and Design Considerations
		10.1 Introduction
		10.2 Precipitation and Coprecipitation
		10.3 MBP Development
			10.3.1 Process Overview
			10.3.2 API Properties
			10.3.3 Solubility of API
			10.3.4 Chemical Stability of API
			10.3.5 Assessment of MBP Feasibility Molecular Weight API Hydrophobicity H-bonding Donor and Acceptors
			10.3.6 Polymer Properties
			10.3.7 Drug Loading
			10.3.8 MBP Process Design Solvent Antisolvent Operation Description and Details of Unit Operations
		10.4 In-Process Characterization
			10.4.1 Crystallinity
			10.4.2 Residual Solvent
			10.4.3 Moisture
			10.4.4 Bioburden
			10.4.5 Tiered Testing
		10.5 Characterization of MBP
		10.6 Formulation for Preclinical Toxicology Studies
			10.6.1 Toxicological Vehicle Selection
			10.6.2 Evaluation of MBP Toxicology Formulation Effect of MBP Concentration Effect of Additives
		10.7 Design of Final Dosage Form
		10.8 Examples of Bioavailability Enhancement
		10.9 Challenges and Future Innovation in MBP Technology
		10.10 Summary
	Chapter 11 MBP Technology: Process Development and Scale-Up
		11.1 Introduction
		11.2 Selection of Solvent and Antisolvent
			11.2.1 Solvent
			11.2.2 API and Polymer Physicochemical Properties
			11.2.3 Concentration in Solution
			11.2.4 Stability of API/Polymer Solution
			11.2.5 Solution Preparation
			11.2.6 Key Characteristics of the Final Solution
			11.2.7 Antisolvent
			11.2.8 Key Characteristics of the Antisolvent
		11.3 MBP Manufacturing
			11.3.1 General Considerations
			11.3.2 Precipitation Technique
			11.3.3 Processing Conditions for High-Shear Precipitation
			11.3.4 High-Shear Mixing-Based Processes Continuous Process Semi-Batch Process
			11.3.5 Mixing Tools
			11.3.6 Ratio of API/Polymer Solution (Solvent)/Antisolvent
			11.3.7 Isolation and Washing of MBP
			11.3.8 Drying
			11.3.9 Milling and Size Reduction
		11.4 Common Issues and Troubleshooting
		11.5 Summary and Conclusions
	Chapter 12 Pharmaceutical Development of MBP Solid Dispersions: Case Studies
		12.1 Introduction
		12.2 Factors to Consider in MBP Development
		12.3 MBP Preparation and Characterization
		12.4 Pharmaceutical Development of MBP
			12.4.1 Polymer Selection and Drug Loading
			12.4.2 Effect of Processing Technologies on MBP Stability
			12.4.3 MBP Particulate Properties: Effect on Mechanical Properties, Downstream Processing, and Dissolution
			12.4.4 Effect of Moisture Content and Crystallinity on Dissolution of MBP
		12.5 Case Studies of MBP of Poorly Soluble Drugs
			12.5.1 MBP Case A
			12.5.2 MBP Case B
			12.5.3 MBP Case C
			12.5.4 MBP Case D
			12.5.5 MBP Case E
		12.6 Summary and Conclusions
	Chapter 13 Downstream Processing Considerations
		13.1 Introduction
		13.2 Downstream Processing of Hot-Melt Extrudates
			13.2.1 Powder Blends and Direct Compression
			13.2.2 Film Coating
		13.3 Downstream Processing of Spray-Dried Powders
			13.3.1 Powder Blends, Dry Granulation and Compression
			13.3.2 Fluid Bed Coating/Layering and Spray Granulation
			13.3.3 Film Coating
		13.4 Downstream Process of MBP
			13.4.1 Powder Blend, Dry Granulation and Compression
			13.4.2 Film Coating
		13.5 Downstream Processing of Mesoporous Silica-Based Systems
			13.5.1 Powder Blends, Dry Granulation and Direct Compression
			13.5.2 Wet Granulation as Alternative Granulation Technique
			13.5.3 Modification of the Release Profile
		13.6 Summary and Conclusion
Part III Characterization
	Chapter 14 Structural Characterization of Amorphous Solid Dispersions
		14.1 Introduction
		14.2 Differential Scanning Calorimetry (DSC) Studies of ASD
			14.2.1 Glass Fragility, Molecular Mobility, and Enthalpy Recovery
			14.2.2 Molecular Miscibility and Compositional Homogeneity
			14.2.3 Crystallization, Melting, Crystallinity, and Mixing Interactions in ASD
		14.3 Isothermal Microcalorimetry (IMC) Studies of ASD
			14.3.1 Enthalpy Relaxation Studies on Amorphous Pharmaceuticals by IMC
			14.3.2 Crystallization Kinetics of and Crystallinity in Amorphous Systems by IMC
		14.4 Powder X-ray Diffractometry (pXRD) and X-ray Scattering
			14.4.1 Local Structure of Amorphous Pharmaceuticals Using Total X-ray Scattering
			14.4.2 Molecular Miscibility in ASD Using pXRD and Computational Analysis
			14.4.3 Crystallization Studies and Crystallinity of Amorphous Systems Using pXRD
		14.5 Gravimetric Vapor Sorption (GVS)
		14.6 Other Techniques
		14.7 Regulatory Perspective of ASD Analysis
	Chapter 15 Dissolution of Amorphous Solid Dispersions: Theory and Practice
		15.1 Introduction
		15.2 Regulatory Quality Control Dissolution Method
		15.3 Amorphous State and Solid Dispersion
		15.4 Theoretical Aspects of Dissolution Testing of Amorphous Drugs
			15.4.1 Solubility and Dissolution of Amorphous Compoundsand Solid Dispersions
			15.4.2 Solution-Mediated Transformation During Dissolution
			15.4.3 Crystallization During Dissolution
			15.4.4 Supersaturation of Amorphous Systems During Dissolution
		15.5 Factors That Influence Dissolution of Amorphous Drug Products
			15.5.1 Formulation Factors
			15.5.2 Manufacturing Factors Which Influence Solid-State Properties
		15.6 Dissolution Case Studies to Guide Formulation Development
			15.6.1 Between Amorphous and Crystalline Phase
			15.6.2 Between Different Temperatures and Polymers
			15.6.3 Dissolution of Salts Weak Bases Weak Acids
			15.6.4 Biorelevant Dissolution Testing of Amorphous Solid Dispersions
		15.7 IVIVCs of Amorphous Formulations
		15.8 Conclusion
	Chapter 16 Stability of Amorphous Solid Dispersion
		16.1 Introduction
		16.2 Factors Affecting the Stability of Amorphous Solid Dispersion (ASD)
			16.2.1 Thermodynamic Aspect
			16.2.2 Kinetic Driving Force: Molecular Mobility Temperature Effect on Mobility Moisture/Water Effect on Mobility Molecular Mobility and Phase Separation
			16.2.3 Processing Methods
			16.2.4 Physicochemical Properties of the Additives: Polymer/Surfactant
		16.3 Principle and Techniques for Prediction of ASD Stability
			16.3.1 API Crystallization Tendency
			16.3.2 API and Additive Miscibility
			16.3.3 Molecular Mobility Estimation of Formulated ASD Molecular Mobility Measured by DSC Molecular Mobility Measured by Dielectric Spectroscopy IMC
			16.3.4 Prediction of Physical Stability by Detection of Phase Separation and Crystallization Phase Separation Detection by Atomic Force Microscopy Phase Separation Detection by Raman Mapping and IR Phase Separation Detection by Tg Change Crystallization Tendency Measured by X-Ray Diffraction Crystallization Tendency Measured by Inverse Gas Chromatography
		16.4 Stability Programs
	Chapter 17 Regulatory Considerations in Development of Amorphous Solid Dispersions
		17.1 Introduction
		17.2 NDA Versus ANDA
		17.3 Quality by Design
			17.3.1 Quality Target Product Profile
			17.3.2 Critical Quality Attributes Drug Substance Polymers and/or Excipients Amorphous/Crystalline Ratio Dissolution
			17.3.3 Manufacturing Process
			17.3.4 Design Space
			17.3.5 Control Strategy
		17.4 Conclusion
Part IV Emerging Technologies
	Chapter 18 KinetiSol®-Based Amorphous Solid Dispersions
		18.1 Background
		18.2 KinetiSol Fundamentals
		18.3 Process Development and Manufacturing with KinetiSol
		18.4 Novel Attributes of KinetiSol for the Processing of ASDs
			18.4.1 KinetiSol Processing of High-Melting-Point Drugs
			18.4.2 KinetiSol Processing of Thermally Labile Drugs
			18.4.3 KinetiSol Processing of Thermally Sensitive, Highly Viscous Polymer Systems Without Plasticizers
			18.4.4 KinetiSol Processing With a Non-Thermoplastic Polymer for Improved Homogeneity
		18.5 Summary
	Chapter 19 Amorphous Solid Dispersion Using Supercritical Fluid Technology
		19.1 Introduction
		19.2 Operations Where SCF Acts as a Solvent
			19.2.1 Rapid Expansion of Supercritical Solvent (RESS)
			19.2.2 RESS Applications
		19.3 Operations Where SCF Acts as an Antisolvent
			19.3.1 Mechanism of Particle Formation in GAS, SAS/ASES
			19.3.2 Applications of GAS, SAS and ASES
		19.4 Solution-Enhanced Dispersion by Supercritical Fluids (SEDS)
		19.5 Operations Where SCF Acts as Solute (Particles from Gas Saturated Solution)
		19.6 Conclusions
Part V Material Advances
	Chapter 20 Supersolubilization by Using Nonsalt-Forming Acid-Base Interaction
		20.1 Introduction
		20.2 Modulation of Microenvironmental pH
			20.2.1 Microenvironmental pH
			20.2.2 Modulation of Microenvironmental pH by Salt Formation
			20.2.3 Modulation of Microenvironmental pH by Using pH Modifiers
			20.2.4 Use of pH Modifiers in Solid Dispersion
		20.3 Supersolubilization and Amorphization by Acid--Base Interaction
			20.3.1 Theory of Supersolubilization
		20.4 Development of Solid Dispersion by Supersolubilization
		20.5 Concluding Remarks
	Chapter 21 Stabilized Amorphous Solid Dispersions with Small Molecule Excipients
		21.1 Introduction to Small Molecules as Carriers in Solid Dispersions
		21.2 Case Studies
			21.2.1 Combinations with Citric Acid
			21.2.2 Combinations with Sugar Molecules
			21.2.3 Co-Amorphous Drug--Drug Combinations Co-Amorphous Drug Composites for Pulmonary Delivery Co-Amorphous Indomethacin--Ranitidine HCl Systems Co-Amorphous Naproxen--Cimetidine Systems Co-amorphous Indomethacin--Naproxen Systems Co-amorphous Glipizide--Simvastatin Systems
			21.2.4 Co-Amorphous Drug-Amino Acid Formulations Receptor Amino Acids as Stabilizers of Co-amorphous Mixtures Combinations of Various Amino Acids to Improve the Dissolution Rate
		21.3 The Possibility of Co-crystal Formation with Low Molecular Weight Excipients
		21.4 Conclusion and Future Perspectives
	Chapter 22 Mesoporous ASD: Fundamentals
		22.1 Introduction
		22.2 Ordered Mesoporous Materials: From MCM-41 to NFM-1
		22.3 Characterisation of Mesoporous Materials
		22.4 Properties of Mesoporous Materials Relevant to Life Sciences
		22.5 Toxicological Implications of Mesoporous Materials
		22.6 Loading Drugs into Mesoporous Materials
		22.7 Fundamentals of Release
		22.8 Matters of High Activity Antiretroviral Therapy (HAART): A Case Study
		22.9 Conclusions and Future Perspectives
	Chapter 23 Mesoporous Silica Drug Delivery Systems
		23.1 Introduction
		23.2 History
		23.3 MPS Materials
		23.4 Synthesis of MPS
			23.4.1 Synthesis of Non-Ordered MPS (MSG)
			23.4.2 Synthesis of OMS
		23.5 Applications of MPS in Drug Delivery
			23.5.1 Delivery of Poorly Soluble Drugs
			23.5.2 Amorphous Stability Improvement
			23.5.3 Controlled/Modified Release and Targeted Drug Delivery
			23.5.4 Protein Drug Delivery
		23.6 Theory of Drug Release from MPS
		23.7 Methods of Drug Loading
			23.7.1 Solvent-Based Methods Solvent Immersion Method Solvent Drying Method Incipient Impregnation Method Spray Drying Method (Takeuchi et al.) Supercritical Fluid Method (Smirnova et al.)
			23.7.2 Solvent-Free Methods Melt Mixing Method (Takeuchi et al.) Co-grinding/Co-milling Method Microwave-Assisted Drug Loading (Waters et al.) Drug Loading During Synthesis (Solgel Process)
		23.8 Factors Affecting Drug Loading and Dissolution
			23.8.1 Effect of Solvent
			23.8.2 Effect of Pore Dimensions, Particle Size, and Surface Area
			23.8.3 Effect of Humidity or Water Content
			23.8.4 Surface Chemistry
		23.9 Techniques of SD Evaluation (Kovacic et al.)
			23.9.1 Particle Size and Morphology
			23.9.2 Differential Scanning Calorimetry and Thermogravimetric Analysis
			23.9.3 X-ray Diffractometry
			23.9.4 Determination of Drug Content and Dissolution
		23.10 Final Dosage Form
		23.11 Biocompatibility, Toxicity, and Regulatory Status of MPS

Similer Documents