Physicochemical principles of pharmacy : in manufacture, formulation and clinical use / Alexander T. Florence, David Attwood.

Format:

Book

Author/Creator:

Florence, A. T. (Alexander Taylor), author.

Attwood, D., author.

Language:

English

Subjects (All):

Pharmaceutical chemistry.

Chemistry, Physical and theoretical.

Physical Description:

1 online resource (xi, 647 pages) : illustrations

Edition:

Sixth edition.

Place of Publication:

London, [England] : Pharmaceutical Press, 2016.

Summary:

This established textbook covers every aspect of drug properties from the design of dosage forms to their delivery by all routes to sites of action in the body.

Contents:

Intro

Contents

Preface

About the authors

Introduction

Physical chemistry and pharmacy

The clinical relevance of physical pharmacy: clinical pharmaceutics

Adjuvants or excipients

Arrangement of the book

Objectives

'Reading' structures and formulae

Chemical structures

Physical equations

1 Solids

1.1 Classification of solids

1.2 Crystalline solids: structure and properties

1.2.1 Crystal structure

Miller indices

1.2.2 Crystal form

Crystallisation and factors affecting crystal form2

Precipitation

Habit modification

1.2.3 Polymorphism4

Pharmaceutical implications of polymorphism

Transformations

Analytical issues

Consequences

1.2.4 Multicomponent crystals

Crystal hydrates and solvates

Pharmaceutical consequences of solvate formation

Cocrystals

1.3 Amorphous solids

1.4 Dissolution of solid drugs

1.5 Biopharmaceutical importance of particle size

1.6 Wetting of powders

1.6.1 Contact angle and wettability of solid surfaces

1.6.2 Wettability of powders

1.7 Freeze drying

1.8 Solid-dosage forms: formulation and manufacture

1.8.1 Excipients

Filler/diluent

Disintegrants

Binders

Lubricants

Glidants

Flavouring agents and colourants

1.8.2 Powder flow

1.8.3 Particle size reduction

1.8.4 Powder mixing and demixing

1.8.5 Granulation

Wet granulation

Stage 1: Granule formation

Extrusion/spheronisation techniques

Bonding mechanisms in wet granulation

Stage 2: Drying and milling

Dry granulation

Bonding mechanisms in dry granulation

1.8.6 Tablet manufacture

Compression and compaction of powders

The compression process

Mechanisms of compression

Tablet coating

Film coating

Film-coating formulations

Solvent

Polymer

Plasticiser

Colourant

Surfactant

Film-coating techniques.

Drum or pan coating

Fluidised-bed coating

Dry coating

Liquid-assisted coating

Thermal adhesion

Electrostatic coating

1.8.7 Capsule manufacture

Chemical and physicochemical properties of gelatin

Hard-capsule manufacture and filling

Manufacture

Filling of powder formulations

Filling of pellets and tablets

Filling of liquids and semisolids

Soft gelatin (softgel) capsule manufacture and filling

Manufacture and filling

1.9 Solid dispersions

1.9.1 Eutectic mixtures

1.9.2 Solid solutions

1.9.3 Eutectics and drug identification

Summary

References

2 Physicochemical properties of drugs in solution

2.1 Concentration units

2.1.1 Weight or volume concentration

2.1.2 Molarity and molality

2.1.3 Milliequivalents

2.1.4 Mole fraction

2.2 Thermodynamics: a brief introduction

2.2.1 Energy

2.2.2 Enthalpy

2.2.3 Entropy

2.2.4 Free energy

2.3 Activity and chemical potential

2.3.1 Activity and standard states

2.3.2 Activity of ionised drugs

2.3.3 Solvent activity

Water activity and inhibition of bacterial growth

Water activity and assessment of pharmaceutical products

2.3.4 Chemical potential

Chemical potential of a component in solution

2.4 Osmotic properties of drug solutions

2.4.1 Osmotic pressure

2.4.2 Osmolality and osmolarity

2.4.3 Clinical relevance of osmotic effects

Tonicity

Volatile anaesthetics

Rehydration solutions

Oral rehydration therapy

2.4.4 Preparation of isotonic solutions

2.5 Ionisation of drugs in solution

2.5.1 Clinical relevance of drug ionisation

2.5.2 Dissociation of weakly acidic and basic drugs and their salts

2.5.3 The effect of pH on the ionisation of weakly acidic or basic drugs and their salts

Weak acids

Weak bases

2.5.4 Ionisation of amphoteric drugs

Ordinary ampholytes.

Zwitterionic ampholytes

Large ΔpKa

Small ΔpKa

2.5.5 Ionisation of polyprotic drugs

2.5.6 Microdissociation constants

2.5.7 pKa values of proteins

2.5.8 Calculation of the pH of drug solutions

Weakly acidic drugs

Weakly basic drugs

Drug salts

2.5.9 Buffer solutions

Buffer capacity

Physiological regulation of acid-base balance

Universal buffers

2.6 Diffusion of drugs in solution

3 Drug stability

3.1 The chemical decomposition of drugs

3.1.1 Hydrolysis

Drugs susceptible to hydrolytic degradation

Controlling drug hydrolysis in solution

Optimisation of formulation

Modification of chemical structure of drug

3.1.2 Oxidation4

Oxidation processes

Drugs susceptible to oxidation

Stabilisation against oxidation

Antioxidants

3.1.3 Isomerisation

3.1.4 Photochemical decomposition10

Stabilisation against photochemical decomposition

3.1.5 Polymerisation

3.2 Kinetics of chemical decomposition in solution

3.2.1 Classifying reactions: the order of reaction

3.2.2 Zero-order reactions

3.2.3 First-order reactions

3.2.4 Second-order reactions

3.2.5 Third-order reactions

3.2.6 Determination of the order of reaction

3.2.7 Complex reactions

Reversible reactions

Parallel reactions

Consecutive reactions

3.3 Solid-dosage forms: kinetics of chemical decomposition

3.3.1 Solids that decompose to give a solid and a gas

3.3.2 Solids that decompose to give a liquid and a gas

3.4 Factors influencing drug stability

3.4.1 Liquid-dosage forms

pH

Temperature

Ionic strength

Solvent effects

Oxygen

Light

Surfactants

3.4.2 Semisolid-dosage forms

3.4.3 Solid-dosage forms

Moisture

Excipients

Light and oxygen

3.5 Stability testing and prediction of shelf-life.

3.5.1 Effect of temperature on stability

Suspensions

Solid state

3.5.2 Other environmental factors affecting stability

Moisture content

3.5.3 Protocol for stability testing

Drug substances

Drug product

Some final points on the stability of drugs

4 The solubility of drugs

4.1 Definitions

4.1.1 Expressions of solubility

4.2 Factors influencing solubility

4.2.1 Structural features and aqueous solubility

Size and shape

Melting point and boiling point

Substituents

Steroid solubility

4.2.2 Hydration and solvation

Hydration of non-electrolytes

Hydration of ionic species: water structure breakers and structure makers

Hydration numbers

Hydrophobic hydration

The solubility of inorganic materials in water

4.2.3 The effect of simple additives on solubility

Solubility products

Common ion effect

Salting in and salting out

4.2.4 The effect of pH on the solubility of ionisable drugs

Acidic drugs

Basic drugs

Amphoteric drugs

Rule of thumb

4.3 Measurement of solubility

4.4 The solubility parameter

4.4.1 Solubility parameters and biological processes

4.5 Solubility in mixed solvents: use of cosolvents

Outline placeholder

Room-temperature ionic liquids

4.6 Cyclodextrins as solubilising agents

Calixarenes

4.7 Solubility problems in formulation

4.7.1 Mixtures of acidic and basic compounds

4.7.2 Choice of drug salt to optimise solubility

4.7.3 Drug solubility and biological activity

4.8 Partitioning

4.8.1 The partition coefficient

4.8.2 Free energies of transfer

4.8.3 Octanol as a non-aqueous phase

4.9 Biological activity and partition coefficients: thermodynamic activity and Ferguson's principle

4.10 Using log P.

4.10.1 The relationship between lipophilicity and behaviour of tetracyclines

4.10.2 Sorption

4.10.3 A chromatographic model for the biophase

4.10.4 Calculating log&amp

thinsp

P from molecular structures

4.10.5 Drug distribution into human milk

5 Surfactants

5.1 Amphipathic compounds

5.2 Surface and interfacial properties of surfactants

5.2.1 Effects of amphiphiles on surface and interfacial tension

5.2.2 Change of surface tension with surfactant concentration: the critical micelle concentration

5.2.3 Gibbs adsorption equation

Application of the Gibbs equation to surfactant solutions

5.2.4 The influence of the surfactant structure on surface activity

5.2.5 Surface activity of drugs

5.2.6 Insoluble monolayers

Experimental study of insoluble films

Monolayer states

Solid or condensed monolayers

Gaseous monolayers

Expanded monolayers

Factors influencing monolayer state

Visualisation of monolayer structures

Polymer monolayers

Lung surfactant monolayers

5.2.7 Pharmaceutical applications of surface film studies

Study of polymers used as packaging materials and film coatings

Cell membrane models

5.2.8 Adsorption at the solid-liquid interface

Adsorption isotherms

Langmuir equation

Freundlich equation

Factors affecting adsorption

Solubility of the adsorbate

Nature of the adsorbent

Some medical and pharmaceutical applications and consequences of adsorption

Adsorption of poisons/toxins

Taste masking

Haemoperfusion

Adsorption in drug formulation

5.3 Micellisation

5.3.1 Water structure and hydrophobic bonding

5.3.2 Theories of micelle formation

5.3.3 Micellar structure

Critical packing parameter

Ionic micelles

Non-ionic micelles.

5.3.4 Factors affecting the critical micelle concentration and micellar size.

Notes:

Includes bibliographical references and index.

Description based on online resource; title from PDF title page (ebrary, viewed April 28, 2016).

ISBN:

9780857112583

0857112589

9780857112590

0857112597

OCLC:

947222597