### Additional Information

#### Book Details

### Abstract

This adaptation *of Bentley's Textbook of Pharmaceutics *follows the same goals as those of the previous edition, albeit in a new look.Â The content of the old edition has beenÂ updated and expandedÂ and several new chapters, viz. Complexations, Stability Testing as per ICH Guidelines, Parenteral Formulations, New Drug Delivery Systems and Pilot Plant Manufacturing, have been included, with an intention to makeÂ the bookÂ more informative for the modern pharmacists.

The book has six sections:

**Section I**deals with the physicochemical principles. Two new chapters: Complexations and ICH Guidelines for Stability Testing, have been added to make it more informative.**Section II**conveys the information regarding pharmaceutical unit operations and processes.**Section III**describes the area of pharmaceutical practice. Extensive recent updates have been included in many chapters of this section. Two new chapters: Parenteral Formulations and New Drug Delivery Systems, have been added.**Section IV**contains radioactivity principles and applications.**Section V**deals with microbiology and animal products.**Section VI**contains the formulation and packaging aspects of pharmaceuticals. Pilot Plant Manufacturing concepts are added as a new chapter, which may be beneficial to readers to understand the art of designing of a plant from the pilot plant model.

### Table of Contents

Section Title | Page | Action | Price |
---|---|---|---|

Front Cover\r | Front Cover | ||

Front Matter \r | i | ||

Copyright \r | iv | ||

Preface To The Adaptation \r | v | ||

Preface To The 8th Edition\r\r | vii | ||

Contributors to the Adaptation | ix | ||

Contributors To The 8th Edition\r\r | xi | ||

Contents \r | xiii | ||

SECTION I Physicochemical Principles\r | 1 | ||

Chapter 1-\r solutions | 3 | ||

COMPOSITION OF SOLUTIONS | 3 | ||

MECHANISM OF SOLVENT ACTION | 3 | ||

MIXED SOLVENTS | 4 | ||

FACTORS THAT INFLUENCE THE RATEAND EXTENT OF SOLUBILITY | 4 | ||

Temperature | 4 | ||

Particle Size | 5 | ||

Solubility and Degree of Saturation | 5 | ||

EXPRESSION OF SOLUBILITY ACCORDINGTO PHARMACOPOEIA | 6 | ||

SOLUTIONS OF SOLIDS IN LIQUIDS | 6 | ||

THE DETERMINATION OF SOLUBILITY | 6 | ||

Analytical Method | 6 | ||

Synthetic Method | 7 | ||

SOLUBILITY CURVES | 7 | ||

SUPERSATURATED SOL | 8 | ||

Methods of Preparing Saturated Solutions | 8 | ||

DISTRIBUTION OF A SOLUTE BETWEENIMMISCIBLE LIQUIDS | 8 | ||

DISTRIBUTION COEFFICIENT | 8 | ||

EXTRACTION WITH IMMISCIBLE SOLVENTS | 9 | ||

COUNTERCURRENT EXTRACTION | 9 | ||

SOLUTIONS OF LIQUIDS IN LIQUIDS | 10 | ||

DETERMINATION OF SOLUBILITY | 10 | ||

Type 1: Mutual Solubility Increases withTemperature | 10 | ||

Type 2: Mutual Solubility Decreases withTemperature | 11 | ||

Type 3: Closed Solubility Curve | 11 | ||

THREE COMPONENT SYSTEMS | 11 | ||

SOLUTIONS OF GASES IN LIQUIDS | 12 | ||

METHODS OF DISSOLVING GASES | 12 | ||

METHODS OF REMOVING DISSOLVED GASES | 13 | ||

SOLVENTS USED IN PHARMACY | 13 | ||

Solvents Used in Manufacturing of Pharmaceuticals | 13 | ||

Solvents for Oral and External Preparations | 13 | ||

Solvents for External Preparations | 13 | ||

Solvents for Injectable Preparations | 13 | ||

MIXED SOLVENTS | 14 | ||

Chapter 2 - pH, EMF and Redox Potentials | 17 | ||

Ionization Constants | 17 | ||

Applications of Dissociation Constant | 17 | ||

Acid Drug | 18 | ||

Basic Drug | 18 | ||

Determination of Dissociation Constant | 18 | ||

Potentiometric titration | 20 | ||

Capillary zone electrophoresis (CE) | 20 | ||

UV-Vis spectrophotometric methods | 20 | ||

Combined methods | 21 | ||

Computational methods | 21 | ||

pKa Determination in Nonaqueous Media | 21 | ||

Buffer Solutions | 22 | ||

Determination of pH Values | 22 | ||

Colorimetric Method for Determining pH | 22 | ||

Electrometric Methods for Determining pH | 23 | ||

significance of pH in Pharmacy | 24 | ||

Redox Potentials | 25 | ||

Chapter 3 - Crystalline Solids | 27 | ||

Polymorphism | 27 | ||

Isomorphous Crystals | 28 | ||

Mechanism of Crystallization | 28 | ||

Crystal Growths in Suspensions | 29 | ||

Precipitation | 30 | ||

Fractional Crystallization | 30 | ||

Water of Crystallization | 30 | ||

Vapour Pressure of Hydrates | 31 | ||

Exsiccation | 31 | ||

Chapter 4 -\rcomplexations | 33 | ||

METAL ION COMPLEXES | 33 | ||

Inorganic-Type Complexes | 34 | ||

Olefin-Type Complexes | 35 | ||

Chelates-Type Complexes | 35 | ||

Aromatic-Type Complexes | 36 | ||

Sandwich compounds | 37 | ||

Sigma ( | 37 | ||

Pi ( | 37 | ||

ORGANIC MOLECULAR COMPLEXES | 38 | ||

Polymer Complexes | 38 | ||

Caffeine and other Drug Complexes | 38 | ||

Picric Acid Complexes | 39 | ||

Quinhydron Complexes | 39 | ||

INCLUSION/OCCLUSIONCOMPOUND COMPLEXES | 39 | ||

Layer-Type Complexes | 39 | ||

Channel Lattice-Type Complexes | 39 | ||

Monomolecular-Type Complexes | 40 | ||

Macromolecular-Type Complexes | 41 | ||

Clathrates-Type Complexes | 41 | ||

ANALYSIS METHODS FORDETERMINATION OF COMPLEXES | 41 | ||

Method of Continuous Variation | 42 | ||

pH Titration Method | 42 | ||

Distribution Method | 43 | ||

Solubility Method | 43 | ||

Spectroscopy and Charge-Transfer Complexation | 44 | ||

Miscellaneous Methods | 44 | ||

PROTEIN BINDING | 45 | ||

APPLICATIONS OF COMPLEXATION | 47 | ||

Chapter 5 -\rinterfacial Phenomena | 49 | ||

INTERMOLECULAR FORCES | 49 | ||

LIQUIDâˆ’GAS AND LIQUIDâˆ’LIQUIDINTERFACES | 50 | ||

Surface Tension and Surface Energy | 50 | ||

Relationship of surface tension and temperature | 50 | ||

Effect of surface curvature | 51 | ||

Interfacial tension | 52 | ||

Cohesion, Adhesion and Spreading | 53 | ||

MEASUREMENT OF SURFACE ANDINTERFACIAL TENSION | 54 | ||

Maximum bubble pressure | 55 | ||

Sessile drop | 55 | ||

Pendant drop | 56 | ||

Drop volume | 57 | ||

du nouy ring tensiometer | 57 | ||

Wilhelmy plate | 58 | ||

SURFACTANTS | 59 | ||

CLASSIFICATION OF SURFACTANTS | 60 | ||

SURFACE ACTIVITY | 60 | ||

The Gibbs equation | 61 | ||

Application of the Gibbs equation to real aqueoussystems | 62 | ||

Verification of the Gibbs equation | 63 | ||

Surface ageing | 64 | ||

BULK PROPERTIES OF SURFACTANTSOLUTIONS | 64 | ||

Theoretical treatment of micelle formation | 65 | ||

Factors affecting micelle formation | 67 | ||

STRUCTURE OF MICELLES AND LIQUIDCRYSTALS | 70 | ||

Stability of micelles | 72 | ||

SOLUBILIZATION | 73 | ||

Factors affecting solubilization | 73 | ||

Ternary phase diagrams | 75 | ||

Pharmaceutical application of solubilization | 76 | ||

INSOLUBLE MONOLAYERS | 77 | ||

Formation of a monolayer | 78 | ||

Surface pressure and its measurement | 78 | ||

Surface Potential and Its Measurement | 79 | ||

Surface Rheology and Its Measurement | 79 | ||

Structure and state of monolayers | 80 | ||

Mixed monolayers | 83 | ||

Macromolecular films | 84 | ||

Biological membranes | 85 | ||

LIQUIDâˆ’SOLID INTERFACE | 86 | ||

Interfacial Energy, Contact Angle and Adhesion | 86 | ||

ADSORPTION ON TO SOLIDS | 86 | ||

PROMOTION OF WETTING | 87 | ||

DETERGENCY | 87 | ||

WATER REPELLENCY | 88 | ||

chapter 6-\r colloidal systems | 91 | ||

LYOPHILIC COLLOIDS | 91 | ||

LYOPHOBIC COLLOIDS | 91 | ||

ASSOCIATION COLLOIDS(AMPHIPHILIC COLLOIDS) | 92 | ||

PREPARATION OF LYOPHOBIC SOLS | 92 | ||

PURIFICATION BY DIALYSIS | 93 | ||

PROPERTIES OF COLLOIDAL SYSTEMS | 95 | ||

Optical Properties | 95 | ||

Ultramicroscope | 95 | ||

Light scattering | 95 | ||

Kinetic Properties | 96 | ||

Ultracentrifuge | 96 | ||

Osmotic pressure | 96 | ||

Diffusion | 96 | ||

Sedimentation | 96 | ||

Viscosity | 97 | ||

Electrical Properties of Colloids | 97 | ||

Ionization | 98 | ||

Adsorption | 98 | ||

Electrophoresis | 98 | ||

Electro-osmosis | 99 | ||

Streaming potential | 100 | ||

Sedimentation potential | 100 | ||

Donnan membrane equilibrium | 100 | ||

PRECIPITATION OF LYOPHOBIC COLLOIDS | 100 | ||

PRECIPITATION OF LYOPHOBIC COLLOIDS | 101 | ||

STABILIZING EFFECT OFLYOPHILIC COLLOIDS | 101 | ||

STABILITY OF COLLOIDS | 102 | ||

GELS | 104 | ||

Preparation of Gels | 104 | ||

Structure of Gels | 104 | ||

Elastic gels | 104 | ||

Rigid gels | 104 | ||

Thixotropic gels | 104 | ||

Syneresis | 105 | ||

PHARMACEUTICAL APPLICATIONSOF COLLOIDS | 105 | ||

Therapeutic Effect | 105 | ||

Blood Plasma Substitutes | 106 | ||

Stability | 106 | ||

Absorption | 106 | ||

Dissolution | 106 | ||

Targeted Drug Delivery | 106 | ||

Solubility Enhancement | 106 | ||

Diagnostic Effect | 107 | ||

Chapter 7-\r adsorption | 109 | ||

TYPES OF ADSORPTION | 109 | ||

Physical Adsorption | 109 | ||

LANGMUIR ADSORPTION ISOTHERM | 109 | ||

BET ADSORPTION ISOTHERM | 110 | ||

Chemisorption | 111 | ||

ADSORPTION FROM SOLUTION | 111 | ||

CHARCOALS | 112 | ||

Medicinal Charcoal | 112 | ||

Decolourizing Charcoals | 112 | ||

Gas-Adsorbing Charcoals | 112 | ||

Standardization of Adsorbents | 112 | ||

APPLICATIONS OF ADSORPTION | 112 | ||

Decolourization | 112 | ||

Adsorption of Water Vapour | 112 | ||

Medicinal Uses | 112 | ||

Adsorption of Pyrogens | 113 | ||

Chapter 8 - \rion Exchange And Chromatography | 115 | ||

ADSORPTION CHROMATOGRAPHY | 115 | ||

Adsorbents | 115 | ||

Solvents | 116 | ||

Apparatus and Experimental Methods | 116 | ||

Location of Zones | 116 | ||

PARTITION CHROMATOGRAPHY | 116 | ||

Types of Partition Column | 117 | ||

Chapter 9 - Diffusion and Dissolution | 137 | ||

Fick's Law of Diffusion | 137 | ||

Fick's First Law | 137 | ||

Fick's Second Law | 137 | ||

Diffusion And Molecular Properties | 137 | ||

Measurement of Diffusion | 137 | ||

Diffusion Through Membranes | 139 | ||

Diffusion of Drugs from Dosage Forms | 139 | ||

Theories of Dissolution | 140 | ||

Film Theory | 140 | ||

Surface Renewal Theory | 141 | ||

Limited Salvation Theory | 141 | ||

Design of Dissolution Apparatus | 142 | ||

Compendial Procedures | 142 | ||

Basket Apparatus (USP Apparatus 1) | 142 | ||

Paddle Apparatus (USP Apparatus 2) | 143 | ||

Reciprocating Cylinder Apparatus (USP Apparatus 3) | 144 | ||

Flow-Through Cell Apparatus (USP Apparatus 4) | 144 | ||

Paddle-Over-Disk Apparatus (USP Apparatus 5) | 146 | ||

Cylinder Apparatus (USP Apparatus 6) | 146 | ||

Reciprocating Holder Apparatus (USP Apparatus 7) | 146 | ||

Intrinsic Dissolution Method (USP) | 146 | ||

Chapter 10 - Rheology | 149 | ||

Elastic Solids | 149 | ||

Modulus of Rigidity | 149 | ||

Bulk Modulus | 149 | ||

Young's Modulus | 149 | ||

Measurement of Elasticity | 150 | ||

Fluids | 150 | ||

Viscosity of Fluids | 150 | ||

Flow Characteristics of Newtonian Fluids | 150 | ||

Effect of Temperature | 151 | ||

Streamline and Turbulent Flow | 151 | ||

Determination of Viscosity | 151 | ||

Capillary Tube Viscometer | 151 | ||

Falling Sphere Viscometer | 153 | ||

Rolling Sphere Viscometer | 154 | ||

Rotating Cylinder Viscometer | 154 | ||

Brookfield Synchrolectric Viscometer | 155 | ||

Rotovisko (Haake) | 156 | ||

Cone and Plate Viscometer (Ferranti-Shirley) | 156 | ||

Extrusion Viscometer | 157 | ||

Creep Testing | 157 | ||

Flow Properties of Non-Newtonian Liquid | 157 | ||

Pseudoplastic Flow | 158 | ||

Plastic Flow | 158 | ||

Dilatancy | 158 | ||

Thixotropy | 159 | ||

Applications of Thixotropy | 159 | ||

Measurement of Thixotropy | 160 | ||

Rheopaxy | 161 | ||

Selection of Viscometer | 161 | ||

Newtonian liquids | 161 | ||

Non-Newtonian liquids | 161 | ||

Rheology of Suspensions | 162 | ||

Rheology of Emulsions | 163 | ||

Rheology of Suspending Agents | 163 | ||

Chapter 11-\r drug Stability | 165 | ||

CHEMICAL DEGRADATION OFPHARMACEUTICAL PRODUCTS | 165 | ||

Hydrolysis | 165 | ||

Oxidation | 166 | ||

Factors affecting the rate of autoxidation | 168 | ||

Isomerization | 168 | ||

Optical isomerization | 169 | ||

Racemization | 169 | ||

Epimerization | 169 | ||

Geometrical isomerization | 169 | ||

Polymerization | 169 | ||

Decarboxylation | 169 | ||

Absorption of Carbon Dioxide | 170 | ||

PHYSICAL FACTORS INFLUENCINGCHEMICAL DEGRADATION | 170 | ||

Temperature | 170 | ||

Moisture | 170 | ||

Light | 171 | ||

Radiation | 171 | ||

APPLICATION OF CHEMICAL KINETICS TODECOMPOSITION OF PHARMACEUTICALPRODUCTS | 172 | ||

Definitions | 172 | ||

Rate of reaction | 172 | ||

Molecularity of reaction | 172 | ||

Order of reaction | 172 | ||

Half-life | 173 | ||

Derivation of the Simpler Orders of Reaction | 173 | ||

First-order reactions | 173 | ||

Half-life of a first-order reaction | 173 | ||

Pseudo-first-order reactions | 173 | ||

Second-order reactions | 174 | ||

Zero-order reactions | 174 | ||

Half-life of a zero-order reaction | 174 | ||

Third-order reactions | 175 | ||

COMPLEXITY OF KINETIC RELATIONSHIPSOCCURRING IN SOME PHARMACEUTICALPRODUCTS | 175 | ||

Influence of Temperature Uponthe Rate of Decomposition | 175 | ||

FACTORS INFLUENCING, AND METHODSOF REDUCING CHEMICAL DEGRADATION | 176 | ||

Hydrolysis | 176 | ||

Adjustment of pH | 176 | ||

Choice of solvent | 176 | ||

Production of an insoluble drug form | 177 | ||

Presence of surface-active agents | 177 | ||

Presence of a complexing agent | 178 | ||

Oxidation | 179 | ||

Presence of antioxidants | 179 | ||

Presence of reducing agents | 181 | ||

Adjustment of pH | 181 | ||

Removal of oxygen | 181 | ||

Presence of surface-active agents | 182 | ||

Photochemical Degradation | 182 | ||

PHYSICAL DEGRADATION OFPHARMACEUTICAL PRODUCTS | 183 | ||

Loss of Volatile Constituents | 183 | ||

Loss of Water | 183 | ||

Absorption of Water | 183 | ||

Crystal Growth | 183 | ||

Polymorphic Changes | 183 | ||

Colour Changes | 184 | ||

STABILITY TESTING | 184 | ||

Accelerated Tests for Chemical Stability | 184 | ||

Limitations of accelerated storage tests for chemicalstability | 186 | ||

Accelerated Tests for Photochemical Stability | 186 | ||

Accelerated tests for moisture absorption | 187 | ||

Accelerated tests for emulsion stability | 187 | ||

Accelerated tests for suspension stability | 187 | ||

Chapter 12 - Ich Guidelines for Stability Testing | 189 | ||

History of Ich | 189 | ||

Need to Harmonize | 189 | ||

Birth of ICH | 189 | ||

Evolution of ICH | 189 | ||

Organization of Ich | 190 | ||

Steering Committee (SC) | 190 | ||

Global Cooperation Group | 190 | ||

The MedDRA Management Board | 190 | ||

Secretariat | 190 | ||

ICH Working Groups | 190 | ||

The Qsem Concept | 191 | ||

Quality Guidelines | 191 | ||

Safety Guidelines | 191 | ||

Efficacy Guidelines | 191 | ||

Multidisciplinary Guidelines | 191 | ||

Zone-Wise Distribution of Countries According to Ich Guidelines | 191 | ||

Stability Programme for a New Drug | 192 | ||

Pre-Formulation and Compatibility | 192 | ||

Preclinical Formulation | 192 | ||

Clinical and NDA Formulation | 192 | ||

Commitment and Product Monitoring | 192 | ||

Steps of Analytical Development and Stability Testing | 192 | ||

Ich Q-Guidelines (Quality) | 193 | ||

Stability | 193 | ||

Analytical Validation | 193 | ||

Impurities | 193 | ||

Pharmacopoeias | 193 | ||

Good Manufacturing Practice | 194 | ||

Pharmaceutical Development | 194 | ||

Pharmaceutical Quality System | 194 | ||

Glossary | 194 | ||

Abbreviations | 197 | ||

SECTION II Pharmaceutical Operations\r | 199 | ||

Chapter 13\r - Extraction | 201 | ||

Leaching Processes | 201 | ||

Maceration | 201 | ||

Modifications of the general process of maceration | 202 | ||

Percolation | 202 | ||

Reserved Percolation | 203 | ||

Choice of Leaching Process | 203 | ||

Factors Affecting the Efficiency of the Leaching Process | 204 | ||

Pretreatment of the raw material and the mechanism of leaching | 204 | ||

The nature of the solvent | 204 | ||

Temperature | 205 | ||

Enzyme activity | 206 | ||

Equipments for Leaching Coarse Solids | 207 | ||

Leaching intermediate solids | 207 | ||

Robert diffusion battery (fixed bed) | 208 | ||

Continuous diffusion batteries | 209 | ||

Oil-Seed Extraction | 210 | ||

Basket extractor | 210 | ||

Rotocel extractor | 211 | ||

Extraction of Fine Material | 211 | ||

The Dorr agitator | 212 | ||

Continuous Leaching of Fine Solids | 212 | ||

The Dorr thickener | 212 | ||

Moving-bed leaching | 213 | ||

Liquid- Liquid Extraction | 214 | ||

Oils | 214 | ||

Vegetable Fixed Oils | 214 | ||

Expression | 214 | ||

Solvent extraction | 214 | ||

Refining | 215 | ||

Animal Oils | 215 | ||

Volatile Oils | 215 | ||

Steam distillation | 216 | ||

Proteins and Polypeptides | 216 | ||

Equipments for Liquid-Liquid Extraction | 216 | ||

Mixer settlers | 217 | ||

Spray and packed extraction towers | 217 | ||

Perforated-plate towers | 217 | ||

Baffle towers | 218 | ||

Agitated tower extractors | 218 | ||

Pulse columns | 218 | ||

Centrifugal extractors | 219 | ||

Auxiliary equipment | 220 | ||

Chapter 14 - Drying | 221 | ||

Theory | 221 | ||

Equipments | 222 | ||

Damp solids | 222 | ||

The tray dryer | 222 | ||

The tunnel dryer | 223 | ||

The rotary dryer | 224 | ||

Infrared heating | 225 | ||

Fluidized bed dryer | 225 | ||

Slurries or Solutions | 226 | ||

The drum dryer | 226 | ||

The spray dryer | 226 | ||

Freeze drying | 226 | ||

chapter 15evaporationthe\r\r | 231 | ||

GENERAL PRINCIPLES OF EVAPORATION | 231 | ||

Vapour Pressure | 231 | ||

Boiling Point | 231 | ||

Effect of Dissolved Substances | 231 | ||

Heat Supply and Vapour Removal | 231 | ||

Heat Transfer | 232 | ||

Film Coefficients | 232 | ||

Separation of Liquid and Vapour | 233 | ||

SMALL-SCALE METHODS | 233 | ||

LARGE-SCALE METHODS | 233 | ||

Heat Transfer Considerations | 233 | ||

Heating by Steam | 234 | ||

Evaporation at Atmospheric Pressure | 234 | ||

Evaporation pans | 234 | ||

Calandria | 235 | ||

Climbing film evaporators | 235 | ||

Horizontal film evaporators | 236 | ||

Forced-circulation evaporator | 236 | ||

Forced-circulation evaporators with externalheating surface | 237 | ||

Multiple-effect evaporator | 237 | ||

Evaporator accessories | 240 | ||

Salt Removal | 242 | ||

Entrainment separators | 243 | ||

Chapter 16 - Distillation | 247 | ||

Simple Distillation Under Atmospheric Pressure | 247 | ||

Small Scale | 247 | ||

Condensers | 247 | ||

Large Scale | 248 | ||

Manesty automatic water still | 248 | ||

Simple Distillation Under Reduced Pressure | 249 | ||

Small Scale | 249 | ||

Vacuum stills | 250 | ||

Fractional Distillation | 251 | ||

Theoretical Considerations and Small-Scale Methods | 251 | ||

Vapour pressure of miscible liquids | 251 | ||

Boiling Point Diagrams and Fractional Distillation | 251 | ||

Azeotropic mixtures | 252 | ||

Ternary mixtures | 252 | ||

Fractionating columns | 253 | ||

Fractional distillation under reduced pressure | 254 | ||

Molecular distillation | 254 | ||

Distillation in Steam | 255 | ||

Theoretical Considerations and Small-Scale Methods | 255 | ||

Vapour pressure of immiscible liquids | 255 | ||

Distillation of immiscible liquids | 255 | ||

Small-scale apparatus | 256 | ||

Large-scale apparatus | 256 | ||

Chapter 17 - Centrifugation | 257 | ||

Theoretical Considerations | 257 | ||

Conversion Between Times Gravity (& | 258 | ||

Laboratory Equipment | 259 | ||

Zonal Centrifugation | 259 | ||

Supercentrifuge | 260 | ||

Large-Scale Equipments | 260 | ||

Vertical Centrifuges | 260 | ||

With perforated basket | 260 | ||

With nonperforated basket | 261 | ||

Horizontal Centrifuges | 262 | ||

Chapter 18 - Filtration | 263 | ||

Mechanism Of Filtration | 263 | ||

Factors Affecting The Rate of Filtration | 263 | ||

Filter Media | 264 | ||

Filter Aids | 264 | ||

Pretreatment of Materials | 264 | ||

Methods of Filtration | 264 | ||

Filter Funnels | 264 | ||

Sintered Glass Filters | 265 | ||

Seitz Filters | 266 | ||

Membrane Filters | 266 | ||

Glass fibre paper | 267 | ||

Filter Press | 268 | ||

Advantages | 269 | ||

Disadvantages | 269 | ||

Metafilter | 269 | ||

Drum Filter | 270 | ||

Air Filtration | 270 | ||

Methods Of Air Filtration | 270 | ||

Chapter 19-\r comminution, Sizing Andhandling Of Powders | 273 | ||

SIZE REDUCTION | 273 | ||

General Principles | 273 | ||

Mechanism of Size Reduction | 273 | ||

Size Distribution During Comminution | 274 | ||

Comminution Machinery | 274 | ||

Mortar and pestle types | 274 | ||

Impact and hammer mills | 275 | ||

Pin mills | 275 | ||

Ball mills | 275 | ||

Vibration mills | 276 | ||

Micronizing | 276 | ||

Other Techniques for Producing Fine Particles | 277 | ||

Precipitation | 277 | ||

Crystallization | 278 | ||

Sieving and sifting | 278 | ||

Sieving | 278 | ||

The Alpine Airjet Sieve | 279 | ||

Classifiers and Sifters | 280 | ||

Determination of Particle Size | 280 | ||

Microscopy | 280 | ||

Sedimentation Method | 281 | ||

Gas Permeability | 282 | ||

Gas Adsorption | 283 | ||

Coulter Counter | 283 | ||

Particle Shape | 283 | ||

HANDLING PROPERTIES | 284 | ||

Sliding and Flow | 284 | ||

Methods for free flowing powders and granules | 284 | ||

Methods for cohesive powders | 285 | ||

Mixing of Powders and Particulate Solids | 286 | ||

Granulation of Powders | 288 | ||

Transport | 288 | ||

Dust Control | 288 | ||

Chapter 20 - Coarse Dispersion | 291 | ||

Emulsions | 291 | ||

Emulsifying Agents | 292 | ||

Preparation and Properties of Emulsions | 292 | ||

o/w Emulsions containing amphipaths | 293 | ||

w/o Emulsions containing amphipaths | 293 | ||

Multiple emulsions | 294 | ||

Emulsions containing hydrophilic colloids | 294 | ||

Emulsions containing solids | 295 | ||

Spontaneous Emulsification and microemulsions | 296 | ||

Stability of Emulsions | 296 | ||

Globule size | 297 | ||

Emulsions in Pharmacy | 298 | ||

Emulsifying Equipment | 298 | ||

Suspensions | 300 | ||

Surface Properties Of The Suspended Solid Particles | 300 | ||

Electrokinetics of the System | 301 | ||

Rate of sedimentation | 302 | ||

Caking of suspensions | 302 | ||

Micromeritics in Suspension | 304 | ||

Particle size Considerations | 304 | ||

Rheology Of Suspensions | 305 | ||

Designing, Preparation and Stabilization of Pharmaceutical Suspensions | 306 | ||

Dispersion | 306 | ||

Flocculation | 306 | ||

Bodying Or Structuring Of Suspensions | 307 | ||

Chapter 21-\r tablets And Capsules | 309 | ||

TABLETS | 309 | ||

Advantages of Tablet Medication | 309 | ||

Disadvantages of Tablet Medication | 309 | ||

Types and Uses of Tablets | 309 | ||

GRANULATION | 309 | ||

The Tablet Compression Cycle | 309 | ||

Essential Granule Properties | 310 | ||

Granulation Processes | 310 | ||

Moist granulation | 310 | ||

Preliminary compression or slugging | 315 | ||

Dry granulation | 316 | ||

Flavours, Lubricants and Disintegrants | 316 | ||

Flavours | 316 | ||

Lubricants | 316 | ||

Disintegrants | 316 | ||

The Compressing Weight | 318 | ||

Dry granulation | 318 | ||

Preliminary compression | 318 | ||

Moist granulation | 319 | ||

PRODUCTION OF TABLETS | 319 | ||

The Single Punch Tablet MachineAssembly | 319 | ||

Adjustments | 319 | ||

Operation | 320 | ||

The Rotary Tablet Machine | 320 | ||

Developments in the Design ofRotary Tablet Machines | 322 | ||

Granule flow | 322 | ||

Die filling | 322 | ||

Removal of air | 322 | ||

Multilayer tablets | 323 | ||

Punches and Dies | 323 | ||

Tabletting Problems | 324 | ||

Binding in the die | 324 | ||

Picking and sticking | 324 | ||

Capping and lamination | 324 | ||

Excessive weight variation | 324 | ||

Fissured or pitted surface | 324 | ||

Soft tablets | 324 | ||

Protracted disintegration | 324 | ||

Mottled tablets | 325 | ||

Variation of medicament content | 325 | ||

Drug instability | 325 | ||

TABLET COATING | 325 | ||

Pan Coating | 325 | ||

Sugar coatings | 325 | ||

Film coating | 326 | ||

Enteric coating | 326 | ||

Automated pan coating | 326 | ||

Fluid-Bed Coating | 327 | ||

Compression Coating | 327 | ||

Compression coating machines | 327 | ||

Requirements for core tablets and coating granules | 328 | ||

Performance | 329 | ||

THE QUALITY CONTROL OF TABLETS | 329 | ||

Uniformity of Diameter | 329 | ||

Tests for Uniformity of Weightand for Medicament Content | 329 | ||

Test for uniformity of weight | 329 | ||

Content of medicament | 330 | ||

Test for Disintegration | 331 | ||

Methods | 331 | ||

Requirements | 331 | ||

Comments on the test | 332 | ||

Colour | 332 | ||

Hardness | 332 | ||

THEORETICAL STUDIES INTABLETTING TECHNOLOGY | 333 | ||

The Compaction Process | 333 | ||

Tablet Hardness | 335 | ||

Effect of compaction pressure | 335 | ||

Effect of materials used and tablet dimensions | 336 | ||

Capping and Lamination | 336 | ||

Granule bonding and relaxation stresses | 336 | ||

Residual die-wall pressure | 336 | ||

Hardness of Materials and Tablet Properties | 337 | ||

Lubrication | 337 | ||

Glidants | 338 | ||

Die-wall lubricants | 339 | ||

Disintegration | 341 | ||

Theory | 341 | ||

Effect of granule properties | 341 | ||

Effects of die-wall lubricants | 341 | ||

Mode of disintegrant action | 342 | ||

CAPSULES | 342 | ||

Soft Capsules | 343 | ||

Hard Capsules | 344 | ||

Quality Control of Capsules | 345 | ||

Disintegration | 345 | ||

Uniformity of filling weight | 345 | ||

Content of medicament | 345 | ||

SECTION III Pharmaceutical Practice3\r | 349 | ||

Chapter 22 - Pharmacopoeias, Formularies And Medicines Legislation\r\r | 351 | ||

The British Pharmacopoeia | 351 | ||

The International Pharmacopoeia | 352 | ||

The European Pharmacopoeia | 353 | ||

The British Pharmaceutical Codex | 353 | ||

The British National Formulary | 353 | ||

The Extra Pharmacopoeia | 354 | ||

Martindale Quarterly 2005 Update | 354 | ||

Martindale Third Quarter 2005 Update | 354 | ||

Martindale Fourth Quarter 2005 Update | 354 | ||

Martindale First Quarter 2006 Update | 354 | ||

Martindale Second Quarter 2006 Update | 354 | ||

Martindale Third Quarter 2006 Update | 355 | ||

Martindale Fourth Quarter 2006 Update | 355 | ||

Martindale First Quarter 2007 Update | 355 | ||

Martindale Second Quarter 2007 Update | 355 | ||

Martindale Third Quarter 2007 Update | 355 | ||

Martindale Fourth Quarter 2007 Update | 355 | ||

Martindale First Quarter 2008 Update | 355 | ||

Martindale Second Quarter 2008 Update | 355 | ||

Martindale Third Quarter 2008 Update | 355 | ||

Martindale Fourth Quarter 2008 Update | 355 | ||

Martindale First Quarter 2009 Update | 355 | ||

Martindale Second Quarter 2009 Update | 355 | ||

Martindale Third Quarter 2009 Update | 355 | ||

Martindale Fourth Quarter 2009 Update | 356 | ||

Martindale First Quarter 2010 Update | 356 | ||

Martindale Second Quarter 2010 Update | 356 | ||

Martindale Third Quarter 2010 Update | 356 | ||

Martindale Fourth Quarter 2010 Update | 356 | ||

Martindale First Quarter 2011 Update | 356 | ||

The United States Pharmacopoeia | 356 | ||

Usp 34-Nf 29 (2011) | 357 | ||

Indian Pharmacopoeia | 357 | ||

Medicines Legislation | 358 | ||

Chapter 23 - Weights And Measures\r\r | 361 | ||

The Metric System | 361 | ||

Length | 361 | ||

Mass | 362 | ||

Capacity | 362 | ||

Liquid Measures | 362 | ||

Analytical Balances and Weights | 362 | ||

General-Purpose Laboratory Balances | 363 | ||

Triple-beam balance | 363 | ||

Mechanical analytical balances | 363 | ||

Electronic balances | 364 | ||

The Weighing Station | 365 | ||

Weighing of Hygroscopic and Volatile Substances | 366 | ||

Chapter 24 - Pharmaceutical Calculations\r\r | 367 | ||

Percentage Solutions | 367 | ||

Expression of Strengths of Intravenous Fluids | 367 | ||

Conversion of Percentage Strength to Millimoles Per Litre | 367 | ||

Osmolarity and Osmolality | 368 | ||

Calculation of Doses for Children | 368 | ||

Square Metre Surface Area Method | 369 | ||

Body surface area | 369 | ||

Reduction and Enlargement of Recipe | 369 | ||

Rule 1 | 369 | ||

Rule 2 | 369 | ||

Calculation by Alligation | 369 | ||

Alligation method | 370 | ||

Calculation by Alligation Alternate or by the Method of Rectangles | 370 | ||

Proof spirit | 370 | ||

Thermometric Scale | 371 | ||

Fahrenheit | 371 | ||

Centigrade/Celsius | 371 | ||

RÃ©aumur | 371 | ||

Kelvin | 371 | ||

Chapter 25 - Prescriptions | 373 | ||

Form of the Prescription | 373 | ||

Language of Prescription Writing | 374 | ||

Dispensing Routine | 374 | ||

Hospital Prescriptions | 375 | ||

Economy In The Use Of Drugs In Hospitals | 376 | ||

Chapter 26 - Oral Preparations\r\r | 377 | ||

Solid Preparations | 377 | ||

Powders | 377 | ||

Dispensing of powders | 377 | ||

Cachets | 379 | ||

Wet seal cachets | 379 | ||

Wet seal cachet machine | 379 | ||

Dry seal cachets | 380 | ||

Dispensing cachets | 380 | ||

Automatic and semiautomatic cachet machines | 380 | ||

Capsules | 381 | ||

Hard capsules | 381 | ||

Enteric coated capsules | 381 | ||

Liquid Preparations | 381 | ||

Mixtures | 381 | ||

Metric medicine bottles | 382 | ||

Labelling | 382 | ||

Medicinal waters | 382 | ||

Infusions | 382 | ||

Suspending agents | 382 | ||

Liquids in mixtures | 383 | ||

Soluble solids in mixtures | 383 | ||

Insoluble solids | 383 | ||

Dispensing in the Metric System | 384 | ||

Interpretation of Prescriptions Written in Apothecary System | 384 | ||

Emulsions | 384 | ||

Hand Emulsifying Machines | 384 | ||

Mortar and Pestle Method | 384 | ||

The dry gum method | 384 | ||

The wet gum method | 385 | ||

Emulsifying Agents | 385 | ||

Powdered tragacanth | 385 | ||

Methylcellulose, BPC | 385 | ||

Agar | 385 | ||

Casein | 386 | ||

Gelatin solution | 386 | ||

Substances Requiring Special Treatment | 386 | ||

Male fern extract | 386 | ||

Paraldehyde | 386 | ||

Chapter 27 - Rectal Administrations\r\r | 387 | ||

Suppositories | 387 | ||

Suppository Bases | 387 | ||

Theobroma oil | 387 | ||

Witepsol Bases | 387 | ||

Glycogelatin Base | 387 | ||

Water-Soluble Bases | 387 | ||

The Fusion Method | 387 | ||

The mould | 387 | ||

Lubricant | 388 | ||

Calculating the quantities | 388 | ||

Making Suppositories with Theobroma oil | 388 | ||

Making Suppositories with Witepsol Base | 389 | ||

The cold compression method | 389 | ||

Glycogelatin suppositories | 389 | ||

Making Suppositories with Glycogelatin Base | 389 | ||

Dispensing Suppositories | 389 | ||

Pessaries | 389 | ||

Enemas | 389 | ||

Evacuant Enemas | 389 | ||

Retention Enemas | 390 | ||

Disposable Enemas | 390 | ||

Chapter 28 - External Preparations\r\r | 391 | ||

Liquid Preparations | 391 | ||

Applications | 391 | ||

Liniments | 391 | ||

Lotions | 391 | ||

Paints | 391 | ||

Ear Drops | 391 | ||

Gargles | 391 | ||

Mouth Washes | 392 | ||

Nasal Drops | 392 | ||

Spray Solutions | 392 | ||

Inhalations | 392 | ||

Solid Preparations | 392 | ||

Ointments | 392 | ||

Hydrocarbon bases | 392 | ||

Absorption bases | 393 | ||

Emulsifying bases | 393 | ||

Water-soluble bases | 393 | ||

Preparation of ointments | 393 | ||

Creams | 394 | ||

Preparation of creams | 394 | ||

Oily creams | 394 | ||

Aqueous creams | 394 | ||

Hydrocortisone cream, BPC | 394 | ||

Dimethicone cream, BPC | 395 | ||

Pastes | 395 | ||

Poultices | 395 | ||

Dusting Powders | 395 | ||

Chapter 29 - Preparations Forr Thethe Eeyee\r\r | 397 | ||

Eye Drops | 397 | ||

Sterility of Eye Drops | 397 | ||

Sterilization of Eye Drops | 397 | ||

Bactericides in Eye Drops | 398 | ||

Hydrogen Ion Concentration | 398 | ||

Tonicity | 399 | ||

Viscosity | 399 | ||

Eye Drop Containers | 399 | ||

Multidose containers | 399 | ||

Preparation of Eye Drops | 399 | ||

Containers | 399 | ||

Sterilization | 400 | ||

Labelling | 400 | ||

Eye Lotions | 401 | ||

Containers for Eye lotions | 401 | ||

Labelling | 401 | ||

Eye Ointments | 401 | ||

Preparation of Eye Ointment | 401 | ||

Water-soluble medicaments | 401 | ||

Water-insoluble medicaments | 401 | ||

Containers for Eye Ointments | 402 | ||

Labelling | 402 | ||

Ocusert | 402 | ||

Diffusion inserts | 403 | ||

Osmotic inserts | 403 | ||

Soft contact lenses | 404 | ||

Soluble Inserts | 404 | ||

Soluble synthetic polymers | 404 | ||

Enteric-coated polymer | 404 | ||

Biodegradable Ophthalmic Inserts | 404 | ||

Chapter 30 - Parenteral Formulations\r\r | 407 | ||

Parenteral Administration of Drugs: A Necessity | 407 | ||

Parenteral Administration Routes | 407 | ||

Subcutaneous route | 407 | ||

Hypodermoclysis | 408 | ||

Intramuscular Route | 408 | ||

The Intravenous Route | 409 | ||

Venoclysis | 409 | ||

IV admixture | 409 | ||

Other Parenteral Routes | 410 | ||

Intra-arterial | 410 | ||

Intrathecal | 410 | ||

Intraepidural | 410 | ||

Intracesternal | 410 | ||

Intra-articular | 410 | ||

Intracardial | 410 | ||

Intrapleural | 410 | ||

Intradermal | 410 | ||

Specialized Large-Volume Parenterals and Sterile Solutions | 410 | ||

Hyperalimentation Solutions | 410 | ||

Cardioplegia Solutions | 411 | ||

Peritoneal Dialysis Solutions | 411 | ||

Irrigating Solutions | 411 | ||

Formulation Of Parenteral Products | 411 | ||

The Active Drug Constituent | 411 | ||

Crystal characteristics | 411 | ||

Chemical Modification of the Drug | 412 | ||

Drug derivitization | 412 | ||

Salt preparation | 412 | ||

Polymorphism | 412 | ||

pH and pK | 412 | ||

Added Substances (Excipients) in Parenteral Formulations | 413 | ||

Antioxidants | 414 | ||

Antimicrobial agents | 414 | ||

Buffers | 414 | ||

Solubilizing agents/emulsifying agents/suspending agents/wetting agents/surfactants | 414 | ||

Surfactants | 414 | ||

Wetting agents | 415 | ||

Emulsifiers | 415 | ||

Tonicity Adjustment Agents | 415 | ||

Chelating Agents and Protectants | 415 | ||

Vehicles | 415 | ||

Aqueous Vehicles | 415 | ||

Water for injection (WFI) | 415 | ||

Sterile water for injection (SWFI) | 415 | ||

Bacteriostatic water for injection (BWFI) | 415 | ||

Sodium chloride injection | 416 | ||

Devices | 416 | ||

Infusion sets | 416 | ||

Materials used | 418 | ||

Tests | 418 | ||

Production | 418 | ||

Facilities | 418 | ||

Arrangement of area | 419 | ||

Flow plan | 419 | ||

Cleanup area | 420 | ||

Compounding area | 420 | ||

Aseptic area | 420 | ||

Environmental control | 420 | ||

Traffic control | 420 | ||

Housekeeping | 420 | ||

Surface disinfection | 421 | ||

Air control | 421 | ||

Laminar-flow environment | 422 | ||

Personnel | 423 | ||

Environmental control evaluation | 423 | ||

Production Procedure | 423 | ||

Cleaning Containers and Equipments | 424 | ||

Handling after cleaning | 425 | ||

Closures | 425 | ||

Equipments | 425 | ||

Product preparation | 426 | ||

Filtration | 426 | ||

Filling | 427 | ||

Liquids | 427 | ||

Solids | 427 | ||

Sealing | 428 | ||

Tip-seal | 428 | ||

Pull seal | 428 | ||

Sterilization | 429 | ||

Quality Control and Assurance | 429 | ||

Sterility Test | 429 | ||

Particulate and Clarity Evaluation | 430 | ||

Chapter 31 - New Drug Delivery Systems | 441 | ||

Levels of Drug Targeting | 442 | ||

Passive Targeting | 442 | ||

Inverse Targeting | 442 | ||

Active Targeting | 442 | ||

Dual Targeting | 442 | ||

Double Targeting | 442 | ||

Combination Targeting | 443 | ||

Problems Associated With Targeted Delivery Systems | 444 | ||

Targeted Drug Delivery systems | 444 | ||

Prodrug | 445 | ||

Liposomes | 445 | ||

Niosomes | 447 | ||

Pharmacosomes | 448 | ||

Virosome | 448 | ||

Immunoliposomes | 448 | ||

-->Microparticles/microspheres | 449 | ||

Methods of Preparation | 449 | ||

Applications | 449 | ||

Nanoparticles | 450 | ||

Solid Lipid Nanoparticles | 450 | ||

Transdermal Drug Delivery system (TDDS) | 451 | ||

Resealed erythrocytes | 452 | ||

Antibody-targeted systems | 452 | ||

Leukocytes | 452 | ||

Platelets | 452 | ||

Micelles | 453 | ||

Polymeric micelles | 453 | ||

Inverse/reverse micelles | 453 | ||

Mixed micelles | 453 | ||

-->Liquid crystals | 454 | ||

Lipoproteins | 454 | ||

Dendrimers | 454 | ||

SECTION IV Radioactivity \r | 457 | ||

Chapter 32 - Radioisotopes | 459 | ||

Radioactivity and Radionuclides Elements of Nuclear Physics | 459 | ||

Definitions | 459 | ||

General Review of Nuclear Structure | 459 | ||

Elementary particles | 459 | ||

A picture of the nucleus | 459 | ||

Nuclear stability | 459 | ||

Radioactivity | 460 | ||

Definition | 460 | ||

Radioactive decay | 460 | ||

Units of radioactivity | 463 | ||

Alpha-decay ( emission) | 463 | ||

Beta-Decay | 464 | ||

Electron capture (EC, K-capture) | 465 | ||

Nuclear fission | 465 | ||

Processes accompanying decay | 465 | ||

Representation of decay: Decay schemes | 465 | ||

Interaction of Radiation with Matter | 466 | ||

Specific ionization | 466 | ||

Particle range | 466 | ||

-Particles | 467 | ||

-Particles | 468 | ||

γ-Radiation | 468 | ||

Production of Radionuclides | 469 | ||

Nuclear reactors | 469 | ||

Reactor Production | 469 | ||

The (n, γ) reaction | 469 | ||

Reactions involving the loss of heavy particles | 469 | ||

Side reactions | 469 | ||

Nuclides from fission products | 470 | ||

Laboratory Neutron Sources | 470 | ||

Cyclotron Irradiations | 470 | ||

Counting Instruments and the Detection of Radiation | 471 | ||

Counting Instruments Dependent on Ionization | 471 | ||

Ion collection phenomena | 471 | ||

Ionization chambers | 472 | ||

Proportional counters | 473 | ||

Geiger-MÃ¼ller counters | 473 | ||

Other types of ionization detector | 475 | ||

Scintillation Counters | 476 | ||

Scintillation phosphors | 476 | ||

Autoradiography | 477 | ||

Contact autoradiography | 477 | ||

Stripping film autoradiography | 477 | ||

Chemical Detection of Radiation | 477 | ||

Electronic Equipment Associated with Counting Devices | 477 | ||

High-voltage supplies | 478 | ||

Preamplifiers | 478 | ||

Amplifiers | 478 | ||

Discriminators and pulse height analysers | 478 | ||

Data registration | 480 | ||

Problems Associated with Counting | 480 | ||

Statistical considerations | 480 | ||

Counter background | 481 | ||

Counter efficiency | 483 | ||

Quenching in liquid phosphor counting | 484 | ||

Selection of a Counting System | 484 | ||

Radiation Hazards and Radiological Safety | 485 | ||

Dose Units | 485 | ||

The Biological Effects of Radiation | 485 | ||

Mechanism of injury | 485 | ||

Radiation effects on the human body | 486 | ||

Background Radiation | 486 | ||

The Control of Radiation Exposure | 487 | ||

Maximum permissible doses | 487 | ||

Estimations of external dose rates | 487 | ||

Shielding | 488 | ||

Estimations of internal dose rates | 489 | ||

The measurement of exposure doses | 489 | ||

The Operation of Radiochemical Laboratories | 491 | ||

Organization | 491 | ||

Laboratory design | 491 | ||

The toxicity grading of radionuclides | 492 | ||

Protection procedures | 493 | ||

Waste control | 494 | ||

Radiochemical Applications | 494 | ||

The Principles of Radiotracer Techniques | 495 | ||

Analytical Applications | 495 | ||

Investigations of analytical procedures | 495 | ||

Radioisotope dilution analysis | 495 | ||

Enzyme assays | 496 | ||

Activation analysis | 496 | ||

Solubility determinations | 496 | ||

Radioimmunoassay | 496 | ||

Medical Applications | 497 | ||

Body composition and body compartments | 498 | ||

Metabolism and turnover | 498 | ||

Circulation and blood flow | 498 | ||

Organ and tumour visualization | 499 | ||

Therapy | 500 | ||

Radiation Sterilization | 502 | ||

The sterilization process | 502 | ||

Factors affecting the radiation sensitivity of microorganisms | 503 | ||

Determination of the sterilizing dose | 505 | ||

Selection of the sterilizing process | 505 | ||

Control procedures | 507 | ||

Advantages of radiosterilization | 507 | ||

Applications | 508 | ||

SECTION V Microbiology and Animal Products\r | 511 | ||

Chapter 33 - Principles of Microbiology | 513 | ||

Bacteria | 513 | ||

Definition | 513 | ||

Morphology and Ultrastructure | 514 | ||

Staining reactions | 514 | ||

The cell wall | 514 | ||

The plasma membrane | 515 | ||

Mesosomes | 515 | ||

Nucleus | 515 | ||

Cytoplasm | 515 | ||

Endospores | 515 | ||

Flagella and motility | 516 | ||

Pili (fimbriae) | 516 | ||

Capsules | 518 | ||

Fungi | 518 | ||

Definition | 518 | ||

General Morphology | 518 | ||

Reproduction | 518 | ||

Asexual | 518 | ||

Sexual | 519 | ||

PROTOZOA | 520 | ||

Definition | 520 | ||

General Characters | 520 | ||

Sarcodina | 520 | ||

Magistophora | 520 | ||

Ciliophora | 520 | ||

Sporozoa | 520 | ||

Nutrition and Energy Provision | 520 | ||

General Requirements | 520 | ||

Inorganic | 521 | ||

Carbon sources | 522 | ||

Nitrogen sources | 522 | ||

Osmotrophy and phagotrophy | 522 | ||

Minor nutritional requirements | 522 | ||

Energy sources | 522 | ||

Classification by Nutritional Type and Energy Source | 522 | ||

The Influence of Nutrient Concentration on Growth Yield | 522 | ||

Factors Affecting Nutrient Requirements and Availability | 523 | ||

Requirements | 523 | ||

Availability | 523 | ||

Some Method of Microbiology | 523 | ||

Microscopy | 523 | ||

Light microscopy | 523 | ||

Electron microscopy | 524 | ||

Cultivation | 524 | ||

Transfer of samples | 524 | ||

Growth media | 525 | ||

Bacterial Counts | 526 | ||

Viable counts | 527 | ||

Measurement of metabolic activity | 528 | ||

Total counts | 529 | ||

Counts of other Microorganisms | 530 | ||

Isolation of Microorganisms in Pure Culture | 530 | ||

Microbial Growth and Reproduction | 530 | ||

Population Growth in Liquid Media | 530 | ||

Change of Total Count During Population Growth | 531 | ||

Continuous Culture | 531 | ||

Factors Influencing Growth and Viability | 532 | ||

Temperature | 532 | ||

Desiccation | 532 | ||

Acidity and alkalinity (pH) | 533 | ||

Oxidation-reduction (O/R) potential | 533 | ||

Methods for producing anaerobiosis | 533 | ||

Reasons for anaerobiosis | 534 | ||

Osmotic pressure | 535 | ||

Electromagnetic radiations | 535 | ||

Surface tension | 536 | ||

Ultrasonic energy | 536 | ||

Pressure | 536 | ||

Energy Yielding Metabolism | 536 | ||

Fermentation and Respiration | 536 | ||

Glucose Fermentation | 536 | ||

Energy from Respiration | 536 | ||

Other Processes Yielding ATP | 537 | ||

Dna Functions and Some Cellular Control Mechanisms | 538 | ||

Aspects of DNA Function | 538 | ||

Protein synthesis | 538 | ||

Control of protein synthesis | 539 | ||

Allosteric Control of Enzyme Activity | 539 | ||

Structure and Composition | 540 | ||

Replication | 540 | ||

Replication of phage | 540 | ||

Replication of other viruses | 543 | ||

Retrovirus Replication Cycle | 543 | ||

Cultivation | 544 | ||

Tissue culture | 544 | ||

Embryonated egg culture | 544 | ||

Whole host inoculation | 544 | ||

Enumeration of Infective Virus | 544 | ||

Reaction to Environmental Conditions | 545 | ||

Chemotherapy of Virus Infections | 545 | ||

Consequences of Retroviral Infection | 545 | ||

Classification of Viruses | 546 | ||

Other Obligate Pathogens | 546 | ||

Rickettsiae | 546 | ||

Chlamydiae (Bedsoniae) | 546 | ||

Mycobacterium leprae | 546 | ||

Bdellovibrio bacteriovorus | 546 | ||

Some Relationships Between Microorganisms and the Human Body: Microbial Diseases and Immunology | 546 | ||

Common Body Flora | 546 | ||

Infection and Pathogenicity | 547 | ||

Invasiveness | 547 | ||

Toxigenicity | 547 | ||

Other mechanisms of pathogenicity | 548 | ||

Host Defences Against Infection | 548 | ||

Constitutive defences | 548 | ||

Inducible Defences: Acquired immunity | 548 | ||

Immunoglobulin production | 549 | ||

Immune tolerance | 550 | ||

Use of immunological products in medicine | 550 | ||

Antigen-Antibody Reactions | 551 | ||

Precipitation and flocculation | 551 | ||

Agglutination | 552 | ||

Lysis and complement fixation | 553 | ||

Immunofluorescence | 553 | ||

Immunity in Virus Diseases | 553 | ||

Undesirable Immunological Reactions | 554 | ||

Hypersensitivity | 554 | ||

Autoimmune Disease | 555 | ||

Blood Group Antigens | 555 | ||

Transplantation immunity | 555 | ||

Immunosuppression | 556 | ||

Epidemiology | 556 | ||

Some definitions | 556 | ||

Factors influencing the spread of disease | 556 | ||

Some potentially epidemic diseases | 556 | ||

Antimicrobial Agents: Modes of Action and Resistance | 558 | ||

Substances affecting metabolism | 558 | ||

Drug Resistance in Bacteria | 558 | ||

Biochemical mechanisms | 558 | ||

Genetic basis of drug resistance | 559 | ||

The Clinical Problem | 559 | ||

Identification of Microorganisms | 559 | ||

Eukaryotic microorganisms | 561 | ||

Viruses | 561 | ||

Bacteria | 561 | ||

Chapter 34 - Disinfection | 563 | ||

Definitions and Terminology | 563 | ||

Disinfectants | 563 | ||

No ideal disinfectant exists. | 564 | ||

Mode of Action of Disinfectants | 564 | ||

Properties of Disinfectants | 565 | ||

Phenols | 566 | ||

Alcohols | 567 | ||

Aldehydes | 567 | ||

Dyes | 567 | ||

Surface-active compounds | 568 | ||

Halogens | 569 | ||

Metals | 570 | ||

Guanidines and amidines | 570 | ||

Furan derivatives | 571 | ||

Quinoline and isoquinoline derivatives | 571 | ||

Factors Affecting Disinfectant Action | 571 | ||

Time of contact | 571 | ||

Concentration of disinfectant | 572 | ||

Temperature | 573 | ||

Test organism | 574 | ||

Pressure of organic matter and other inactivators | 574 | ||

Hydrogen ion concentration | 574 | ||

Surface tension and effect of formulation | 574 | ||

Chemical structure of the disinfectant | 576 | ||

Nature of the surface to be disinfected | 576 | ||

Potentiation, synergism and antagonism of disinfectants | 576 | ||

Disinfectant Evaluation | 577 | ||

Tests Applied to Liquid Disinfectants | 577 | ||

Assessment of bacteriostatic activity | 577 | ||

Assessment of bactericidal activity | 579 | ||

Merits of phenol coefficient tests | 580 | ||

Deficiencies of phenol coefficient tests | 580 | ||

Tests Applied to Semisolid Antibacterial Formulations | 583 | ||

Assessment of bacteriostatic activity | 584 | ||

Assessment of bactericidal activity | 584 | ||

Tests Applied to Solid Disinfectants | 584 | ||

CHAPTER 35 - Sterilization | 587 | ||

Definitions | 587 | ||

Thermal Resistance of Microorganisms | 587 | ||

Thermal death time | 587 | ||

Death rate of microorganisms | 587 | ||

Decimal reduction time (D) | 588 | ||

Inactivation factor | 588 | ||

z value | 588 | ||

Choice of test organism | 588 | ||

Acceptable Standards for Sterilization Procedures | 589 | ||

Terminology | 589 | ||

Methods of assessment | 589 | ||

Sterilization Processes | 589 | ||

Sterilization with Moist Heat | 589 | ||

Immersion in boiling water | 589 | ||

Treatment with steam at elevated pressure | 590 | ||

Autoclaving | 590 | ||

Principles of steam sterilization | 590 | ||

Saturated steam | 590 | ||

Superheated steam | 590 | ||

Tolerable degrees of superheating | 591 | ||

Wet and dry steam | 591 | ||

Design and Operation of Autoclaves | 591 | ||

Portable autoclaves | 591 | ||

Horizontal large-scale autoclaves | 592 | ||

Automatic process control | 595 | ||

Performance tests | 595 | ||

Other autoclaving methods | 596 | ||

Other Methods of Sterilization with Moist Heat | 597 | ||

Dry Heat Sterilization | 597 | ||

Resistance to dry heat | 597 | ||

Official requirements | 597 | ||

Hot air oven | 597 | ||

Infrared conveyor ovens | 598 | ||

Thermal heating blocks | 599 | ||

Radiofrequency induction heating | 599 | ||

Sterilization by Filtration | 599 | ||

Advantages | 599 | ||

Disadvantages | 599 | ||

Bacteria-proof filters for solutions | 600 | ||

Standardization and testing of filters | 603 | ||

Filtration of Air | 604 | ||

Gaseous Sterilization | 605 | ||

Ethylene Oxide | 605 | ||

Factors affecting sterilizing efficiency | 605 | ||

Apparatus and techniques for ethylene oxide sterilization | 606 | ||

Control of the process | 606 | ||

Other Gaseous Sterilants | 607 | ||

Preparation Of Sterile Medicaments | 607 | ||

Types of Sterile Medicament | 607 | ||

Parenteral injections | 607 | ||

Pyrogens | 608 | ||

Water for Injections (Aqua injectabilia, EP) | 609 | ||

Aseptic Technique | 609 | ||

Sources of contamination | 609 | ||

Methods of minimizing the contamination level | 609 | ||

Containers for parenteral injections | 610 | ||

Ampoules | 610 | ||

Single-dose containers for large volumes | 611 | ||

Multiple-dose containers | 611 | ||

Choice of sterilizing method | 612 | ||

Chapter 36 - Microbial Contamination Control And Sterility Testing\r\r | 615 | ||

Quality Control | 615 | ||

Principles | 615 | ||

Microbial Contamination of Nonsterile Products | 615 | ||

Extent of contamination | 615 | ||

Nature of the contamination | 616 | ||

Methods | 617 | ||

Ophthalmic ointments | 618 | ||

Sterility Testing | 618 | ||

Sample size | 618 | ||

Statistical considerations | 618 | ||

Media | 619 | ||

Media for penicillins and cephalosporins | 621 | ||

Suitability of media | 621 | ||

Samples possessing inherent or added antimicrobial activity | 622 | ||

Controls | 623 | ||

Time and temperature of incubation | 623 | ||

Recording and interpretation of the test | 624 | ||

Special modifications of technique | 624 | ||

chapter 37 vaccines and sera \r\r | 627 | ||

Historical Review | 627 | ||

The Immune State | 628 | ||

Natural Resistance | 628 | ||

Immunity After Infection | 628 | ||

Action of Humoral Immunity | 629 | ||

Response of the Subject | 629 | ||

Maternal antibody inhibition | 629 | ||

Age of the infant | 630 | ||

Nature of the Antigen | 630 | ||

Concentration | 630 | ||

Adjuvants | 630 | ||

Live or dead antigens | 631 | ||

Immune Sera | 631 | ||

Potency Assay of Immune Sera | 631 | ||

Vaccines | 632 | ||

Laboratory Control | 632 | ||

Bacterial vaccines and toxoids | 632 | ||

Bacterial seed strain | 632 | ||

Substrate for bacterial growth | 633 | ||

Safety tests of bacterial vaccines | 633 | ||

Virus vaccines | 633 | ||

Virus strain used for vaccine production | 633 | ||

Tests on cell substrate | 633 | ||

Tests on virus harvest | 634 | ||

Potency tests | 635 | ||

Vaccines Used in Prophylaxis | 636 | ||

Bacterial Vaccines | 636 | ||

Anthrax | 636 | ||

Cholera | 636 | ||

Diphtheria | 636 | ||

Leprosy | 636 | ||

Plague | 636 | ||

Tetanus | 636 | ||

Tuberculosis | 637 | ||

Typhoid | 637 | ||

Whooping Cough | 637 | ||

Virus Vaccines | 637 | ||

Influenza | 637 | ||

Parainfluenza | 638 | ||

Respiratory syncytial virus | 638 | ||

Adenovirus | 638 | ||

Rhinovirus | 638 | ||

Smallpox | 638 | ||

Chickenpox (varicella) | 638 | ||

Herpes simplex (febrillis) | 638 | ||

Yellow fever | 638 | ||

Western equine encephalomyelitis (WEE) and Eastern equine encephalomyelitis (EEE) | 638 | ||

Japanese B encephalitis (JBE) | 639 | ||

Russian spring summer encephalitis (RSSE) or tick-borne encephalitis (TBE) | 639 | ||

Dengue | 639 | ||

Rift valley fever | 639 | ||

Louping-Ill | 639 | ||

Poliomyelitis | 639 | ||

Rabies | 640 | ||

Hepatitis | 640 | ||

Measles (rubeola) | 640 | ||

German measles (rubella) | 641 | ||

Mumps (infective parotitis) | 641 | ||

Trachoma | 641 | ||

Balance of Risks | 641 | ||

Chapter 38 - Antibiotics\r\r | 643 | ||

Antibiotic Research and Production | 643 | ||

The Search for a New Antibiotic | 643 | ||

Antibiotic Production | 644 | ||

Antibiotic Assay | 645 | ||

Penicillins | 646 | ||

Penicillin Breakdown | 646 | ||

Applications of Benzylpenicillin | 646 | ||

Forms of benzylpenicillin | 647 | ||

Assay of benzylpenicillin | 647 | ||

Phenoxymethylpenicillin | 647 | ||

Applications of phenoxymethylpenicillin | 647 | ||

Forms of phenoxymethylpenicillin | 647 | ||

Assay of phenoxymethylpenicillin | 647 | ||

Semisynthetic Penicillins | 647 | ||

Applications of the semisynthetic penicillins | 648 | ||

Forms of the semisynthetic penicillins | 648 | ||

Cloxacillin | 648 | ||

Assay of the semisynthetic penicillins | 649 | ||

Cephalosporins | 649 | ||

Applications of Cephalosporins | 649 | ||

Cephaloridine | 649 | ||

Cephalothin | 649 | ||

Cephaloglycine | 649 | ||

Cephalexin | 649 | ||

Forms of the Cephalosporins | 650 | ||

Cephaloridine | 650 | ||

Cephalothin | 650 | ||

Cephaloglycine | 650 | ||

Assay of Cephalosporins | 650 | ||

CHLORAMPHENICOL | 650 | ||

Applications of Chloramphenicol | 650 | ||

Forms of Chloramphenicol | 650 | ||

Polypeptide Antibiotics | 650 | ||

Bacitracin | 650 | ||

Applications of bacitracin | 650 | ||

Polymyxin | 650 | ||

Polymyxin B | 650 | ||

Pyocyanea | 650 | ||

Colistin | 650 | ||

Carbohydrate Antibiotics | 650 | ||

Streptomycin | 651 | ||

Applications of streptomycin | 651 | ||

Assay of streptomycin | 651 | ||

Neomycin | 651 | ||

Applications of neomycin | 652 | ||

Kanamycin | 652 | ||

Applications of kanamyci | 652 | ||

Gentamicin | 652 | ||

Applications of gentamicin | 652 | ||

Tetracyclines | 652 | ||

Chlorteracycline | 653 | ||

Oxytetracycline | 653 | ||

Tetracycline | 653 | ||

Demethylchlortetracycline | 653 | ||

Methacycline | 653 | ||

Applications of the Tetracyclines | 654 | ||

Forms of the Tetracyclines | 654 | ||

Chlortetracycline | 654 | ||

Oxytetracycline | 654 | ||

Tetracycline | 654 | ||

Demethylchlortetracycline | 654 | ||

Doxycycline | 654 | ||

Methacycline | 654 | ||

Erythromycin | 654 | ||

Applications of Erythromycin | 654 | ||

Forms of Erythromycin | 654 | ||

Novobiocin | 654 | ||

Fusidic Acid | 654 | ||

Applications of Fusidic Acid | 655 | ||

Griseofulvin | 655 | ||

Applications of Griseofulvin | 655 | ||

Assay of Griseofulvin | 655 | ||

Lincomycin | 655 | ||

Applications of Lincomycin | 655 | ||

Clindamycin | 655 | ||

Vancomycin | 656 | ||

Applications of Vancomycin | 656 | ||

Rifampicin | 656 | ||

Applications of Rifampicin | 656 | ||

Chapter 39 - Blood Products And Plasma Substitutes\r\r | 657 | ||

Whole Human Blood Bp | 657 | ||

Deterioration During Storage | 657 | ||

Bacterial Contamination | 657 | ||

Transmission of Disease from the Donor | 657 | ||

Sensitization to Blood Group Antigens | 657 | ||

Bleeding | 658 | ||

Uses | 658 | ||

Concentrated Human Red Blood Corpuscles Bp | 658 | ||

Concentrates of Platelets and White Blood Corpuscles | 658 | ||

Plastic Transfusion Equipment: Plasmapheresis | 658 | ||

Plasma, Serum and Plasma Fractions | 659 | ||

Dried Human Plasma, BP | 659 | ||

Storage | 660 | ||

Labelling | 660 | ||

Chapter 40 - Sutures and Ligatures | 669 | ||

Absorbable | 669 | ||

Nonabsorbable | 669 | ||

Standards and Legal Requirements for Sutures and Ligatures | 669 | ||

Absorbable Materials | 670 | ||

Surgical Catgut | 670 | ||

Splitting | 671 | ||

Cleaning of submucosa | 671 | ||

Spinning | 671 | ||

Polishing | 672 | ||

Gauging | 672 | ||

Standards | 672 | ||

Sterilization of Catgut | 673 | ||

Chemical sterilization | 673 | ||

Heat sterilization | 674 | ||

Radiation sterilization | 674 | ||

Reconstituted Collagen | 674 | ||

Synthetic Absorbable Material | 674 | ||

Kangaroo Tendon | 674 | ||

Ribbon Gut | 675 | ||

Fascia Lata | 675 | ||

Absorption of Catgut in the Body | 675 | ||

Nonabsorbable Sutures | 675 | ||

Silk | 675 | ||

Linen | 676 | ||

Polyamides | 676 | ||

Polyester | 676 | ||

Stainless Steel Wire | 676 | ||

Suture Clips | 676 | ||

Wire Staples | 677 | ||

Surgical Needles | 677 | ||

SECTION VI Formulation And Packing\r | 679 | ||

Chapter 41 - Formulation | 681 | ||

Economic Large-Scale Manufacture | 681 | ||

Acceptability | 681 | ||

Flavour and perfumes | 681 | ||

Colours | 682 | ||

Stability | 682 | ||

Anhydrous vehicles | 683 | ||

Suspensions | 683 | ||

Preservation against Microbial Spoilage | 684 | ||

Physical methods of protection | 685 | ||

Chemical methods of preservation | 685 | ||

Selection of antimicrobial preservatives | 685 | ||

Correct dose | 688 | ||

Therapeutic Effectiveness | 689 | ||

Biological | 689 | ||

Chemical | 689 | ||

Pharmaceutical | 690 | ||

Biological availability of drugs from conventional preparations | 691 | ||

The variable (K) | 693 | ||

Dissolution rate tests | 693 | ||

Modification of the onset, intensity and duration of therapeutic action | 694 | ||

Formulation of prolonged action preparations | 696 | ||

Other long-acting preparations | 698 | ||

Chapter 42 - Pharmaceutical Aerosols | 703 | ||

Categories | 703 | ||

Topical preparations | 703 | ||

Local analgesics | 703 | ||

Local anaesthetics | 703 | ||

Antiseptic and skin sterilizers | 703 | ||

Skin dressings | 703 | ||

Fungicidal agents | 703 | ||

Antiparasitic agents | 703 | ||

Antibiotics | 703 | ||

Preparations for administration to body cavities | 703 | ||

Advantages and Disadvantages of Aerosols | 704 | ||

Advantages | 704 | ||

Disadvantages | 704 | ||

BASIC AEROSOL TECHNOLOGY | 705 | ||

Aerosol Systems | 705 | ||

Propellants | 706 | ||

Liquefied gases | 706 | ||

Calculation of vapour pressure of a mixture of liquefied gases | 706 | ||

Compressed gases | 708 | ||

Containers | 708 | ||

Valves | 709 | ||

Basic Aerosol Formulation | 709 | ||

Factors Affecting Spray Characteristics | 710 | ||

Viscosity | 710 | ||

Vapour pressure of the propellants | 710 | ||

Propellant product ratio | 710 | ||

Presence of solvents | 710 | ||

Temperature | 711 | ||

Aerosol Filling | 711 | ||

Pressure filling with hydrocarbon and fluorohydrocarbon propellants | 711 | ||

Cold filling with hydrocarbon and fluorohydrocarbon propellants | 711 | ||

Testing of Aerosols | 712 | ||

Leakage | 712 | ||

Internal pressure | 712 | ||

Spray pattern | 712 | ||

Discharge rates | 712 | ||

Flammability | 713 | ||

Particle size analysis | 713 | ||

Moisture determination | 713 | ||

Analysis of propellant mixtures | 713 | ||

Aerosols for Oral Inhalation | 713 | ||

Inertial forces | 714 | ||

Uniformity of dosage through the adaptor | 715 | ||

Uniformity of valve delivery | 715 | ||

Chapter 43 - Packaging\r\r | 717 | ||

Packaging Materials | 717 | ||

Metals | 717 | ||

Tin | 717 | ||

Iron | 717 | ||

Aluminium | 718 | ||

Polymers | 718 | ||

Plastics | 719 | ||

Compounding plastics | 720 | ||

Toxicity | 721 | ||

Permeability | 721 | ||

Plastics in the packaging of pharmaceutical products | 721 | ||

Rubber | 722 | ||

Natural rubber | 722 | ||

Synthetic elastomers | 723 | ||

Further processing | 723 | ||

Rubber in the packaging of pharmaceuticals | 724 | ||

Glass | 725 | ||

Structure and composition | 725 | ||

Container production | 727 | ||

Mechanical strength | 727 | ||

Resistant to thermal shock | 728 | ||

Chemical durability | 728 | ||

Flake and spicule formation | 729 | ||

Closures | 730 | ||

Folded seals | 730 | ||

Push-on seals | 731 | ||

Bung seals | 731 | ||

Screw-cap seals | 732 | ||

Fusion seals | 732 | ||

Package Testing | 732 | ||

Filling | 733 | ||

Liquids | 733 | ||

Semisolids | 733 | ||

Powders | 734 | ||

Unit-dose products | 734 | ||

Repackaging | 734 | ||

Chapter 44: - Pilot Plant Manufacturing\r\r | 737 | ||

General Considerations | 737 | ||

Reporting Responsibility | 737 | ||

Personnel Requirement | 737 | ||

Space Requirement | 738 | ||

Administration and information process | 738 | ||

Physical testing area | 738 | ||

Standard pilot plant equipment floor space | 738 | ||

Storage area | 738 | ||

Review of the Formula | 738 | ||

Raw Materials | 738 | ||

Processing Equipments | 738 | ||

Process Evaluation | 739 | ||

Preparation of Master Manufacturing Procedure | 739 | ||

GMP Considerations | 739 | ||

Transfer of Analytic Methods to Quality Assurance | 740 | ||

Solid Dosage Forms | 740 | ||

Mixing or Blending | 740 | ||

Mixing or blending technique | 740 | ||

Mixing or blending speed | 740 | ||

Mixing or blending time | 740 | ||

Drug uniformity | 740 | ||

Excipient uniformity | 740 | ||

Wet Granulation | 741 | ||

Binder addition | 741 | ||

Binder concentration | 741 | ||

Amount of binder solution/granulating solvent | 742 | ||

Mixing time | 742 | ||

Drying | 742 | ||

Milling | 742 | ||

Dry Blending and Direct Compression | 743 | ||

Dry granulation (slugging) | 743 | ||

Tablet Compression | 743 | ||

Tooling | 744 | ||

Compression speed | 744 | ||

Compression/ejection force | 744 | ||

Tablet Coating | 744 | ||

Tablet properties | 744 | ||

Equipment type | 744 | ||

Coater load | 745 | ||

Pan speed | 745 | ||

Spray guns | 745 | ||

Application/spray rate | 745 | ||

Tablet flow | 745 | ||

Inlet/outlet temperature and air flow | 745 | ||

Coating solution | 745 | ||

Coating weight | 745 | ||

Liquid Dosage Forms | 745 | ||

Contract Manufacture | 748 | ||

Index\r | 749 | ||

A\r | 749 | ||

B\r | 750 | ||

C\r | 750 | ||

D\r | 752 | ||

E\r | 753 | ||

F\r | 754 | ||

G\r | 754 | ||

H\r | 755 | ||

I\r | 755 | ||

J\r | 755 | ||

K\r | 755 | ||

L\r | 755 | ||

M\r | 756 | ||

N\r | 757 | ||

O\r | 757 | ||

P\r | 757 | ||

Q\r | 759 | ||

R\r | 759 | ||

S\r | 759 | ||

T\r | 761 | ||

U\r | 762 | ||

V\r | 762 | ||

W\r | 762 | ||

X\r | 762 | ||

Y\r | 762 | ||

Z\r | 762 |