Formulation

Edited

by

Anne-Marie Pense-Lheritier

WILEY

Table of Contents

Preface Part One: General Information

xi 1
3

Chapter

1. Introduction

Andre CHEYMOL 1.1. Definition 1.2. Historical 3

background impact
of the

3 8
14 structure

1.3. From art to science 1.4. Overview of the economical aforementioned

products 1.5. Book presentation and 1.6. Bibliography

15 16

Chapter 2. Formulation in Major Organic Chemistry

Industries Andre CHEYMOL 2.1. 19

Necessity and concept 2.1.1. Specificities of each industry 2.2. Factors affecting different industries 2.3. Outlining a methodology 2.4. Bibliography

19 20 26 27 30

vi

Formulation

Part Two: Concept and Application

31
33

Chapter 3. Solutions
Anne-Marie Pense-Lheritier 3.1. Introduction
3.1.1. Preamble 3.1.2. Definition

33 33 33
34 35

3.1.3. 3.2.

Approach
water

3.1.4. Choice of solvents

Solubilizing in pH control

35 35 37 37 38 40 43 43 45 46 48 48 49 53

3.2.1. 3.3.

3.2.2. Salts

Solubilizing

in solvents

3.3.1. The dielectric constant 3.3.2. Theoretical 3.4. Processes to

approach: solubility parameters help solubilization

3.4.1. Micellar solubilization agents: surfactants 3.4.2. Microemulsion 3.4.3. Formation of complexes 3.4.4. Solid solutions 3.5. Conclusion 3.6.

Bibliography
4.

Chapter

Dispersions

Gerard HOLTZINGER 4.1. Introduction 4.2. Particles and their 4.2.1. Definition 53

specificities

54 54 56 58 60 61 62 62
63

4.2.2. Size of a particle

4.2.3. Form of the 4.2.4. 4.2.5.

particles

Porosity Specific surface 4.3. Various particle systems and stability issues
4.3.1. Particle systems 4.3.2.

of particles

Stability

of

dispersions theory

4.3.3. Sedimentation
4.3.4. Flocculation and DVLO 4.3.5. Ostwald

65 69 86 89

ripening analysis techniques

4.4.

Dispersion

methods and

Table of Contents

vii

Sampling 4.4.2. Sieving 4.4.3. Microscopy 4.5. Rheology

4.4.1. 4.5.1. Definition

89 90 91 107 107 109 115 115 119

Viscosity 4.5.3. Electroviscosity and electrorheology 4.6. Bibliography

4.5.2.
measurement

Chapter

5. Formulation of Emulsions

Anne-Marie PENSE-LHERITIER 5.1. General aspects of emulsions

5.2. Theoretical

119 the

considerations

on

liquid-liquid

interactions

121 121 122 125 126 127 134 134 136 138 139 139 141 141 142 143 143 144 144 147

5.2.1.

Origin

of the surface effects

5.2.2. Role of modifying agents in surface tension

Developing the emulsion Selecting the fatty phase 5.3.2. Selecting the surfactant 5.4. Stabilizing an emulsion 5.4.1. Creaming, sedimentation, and kinetic stabilization 5.4.2. Flocculation and DVLO theory
5.3. 5.3.1. 5.4.3. Coalescence and 5.4.4. Phase inversion

steric stabilization

5.4.5. Basic rules for emulsification 5.5. Formulation of emulsions 5.5.1. Temperature 5.5.2. Time
5.5.3.

Agitation
on

5.5.4. Controls realized 5.6. Conclusion 5.7.

emulsions

Bibliography
6.

Chapter
6.1.

Suspensions

Gerard HOLTZ1NGER

Dispersion theory

148 148
152 152 153

6.1.1. 6.1.2. 6.1.4.

Wettability Adhesivity of particles Adsorption

6.1.3. Friction forces

viii

Formulation

6.2. Formulation of suspensions 6.2.1. The

155 155 155 157 158 158 159 160 164 164 165 166 166
167

dispersion 6.2.2. Dispersing agents 6.2.3. Agents that limit sedimentation

6.2.4. Fluidifiers 6.3.

medium

Stability

agents of suspensions

6.3.1.

Stabilization through polymers

case case

6.3.2. Structure of

6.4. 6.5.

Specific
Specific

polymeric dispersants of the pharmaceutical realization

of cosmetics

pigments 6.5.2. Organic pigments 6.5.3. Treating pigments 6.6. Using dispersion
6.6.1, Various
6.6.2. 6.7.

6.5.1. Mineral

dispersion steps

167 181
183

Monitoring dispersions Bibliography

Chapter 7. Dispersions in High-Viscosity Mediums: Formulating Polymers

Andre CHEYMOL

185

7.1. Characterization of polymers 7.2. Formulation of polymers:

7.2.1. Basic notion

185

general concerning the properties ruling the

information

198

realization of the formulation 7.2.2. 7.2.3.

7.2.4.

200 200
....

Rheologic behavior: reminder of the first basic laws Rheologic models linking viscosity and shearing rate Measuring polymer viscosity

202

208 211 211

7.3. Thermal behavior 7.3.1. Glass transition fusion

7.3.2. Calorific
mass

capacity:

(in Joule

per 213

Kelvin and per 7.3.3. Thermal 7.4. Heat 7.5. Main

Kg) conductivity
and transmission tools

214 216 218 218

219 221

generation
mixing

7.5.1. Common 7.5.3. 7.7.

principle

7.5.2. Worm drive tools

Mixing
on

7.6. Conclusion

the

polymer

formulation rules

227 227

Bibliography

Table of Contents

ix

Part Three: formulation

of

Major Products

231

Chapter 8. Dosage Form and Pharmaceutical Development

Vincent FAIVRE
8.1.

233

Drugs development

233 233
234 235

drug-product development 8.1.3. Dosage form development 8.2. Case study: development of a dosage form for
8.1.2. Pharmaceutical oral administration
8.2.1. Patients and market 8.2.2. Characteristics of active 8.2.3.

8.1.1. The

246 246

ingredients

246

Manufacturing processes and choice

248

of formulation
8.3.

Monitoring/checking

methods

249 249 250 validations 250 252 253

8.3.1. Cause/effect 8.3.2. P.A.T

8.3.3. 8.4.

diagram

"European pharmacopeia" Bibliography

Chapter

9. Formulation of Cosmetic Products

Caroline ROUSSEAU 9.1. Introduction 9.2. 253 254

the

Specifications 9.3. Development in

9.3.2. 9.3.3.

laboratory

256 257 258 260

9.3.1. Choice of the

ingredients
stability

Realizing

the formula formula

Study of the

9.3.4. Validation of the resilience of the formula with

to micro

regards
261 261 263 265 265 266 267

9.3.5.

organisms Determining the

PAO

9.3.6. Evaluation of the formula 9.4. Industrial fabrication 9.5. Product launch 9.6.

Regulations

9.7. Conclusion

Formulation

Chapter 10. Formulation of Food

Christine CHENE 10.1.

Products

269

Specifications

269 271 271

273

10.2. Constraints
10.2.1.

Regulation

10.2.2. Fabrication and conservation conditions 10.2.3. Cost constraints

278 279 283

10.3. Formulation methodology

Chapter 11. Formulation of Elastomers

Andre CHEYMOL 11.1. Introduction 11.2. Choice of the elastomers
11.2.1. Natural rubber

283
284 284
.

11.2.2.
11.2.3.

11.2.4. 11.2.5. 11.2.6. 11.2.7. 11.2.8.

diene

Styrene butadiene (copolymer of butadiene and styrene) Polybutadiene (butadiene polymer) Synthetic poly isoprene Copolymer of acrylonitrile butadiene Polychloroprene (chloroprene polymer) Polyisobutylene (butyl rubber) Ethylene propylene copolymers, ethylene propylene

285 286
286

286 287 287 288 289 289

copolymers

11.2.9. Silicones
11.2.10.

11.3.

Polyurethanes Adjuvants required

to obtain crucial functions

290 291
302

11.3.1. Reticulation and reticulation modes 11.3.2. Choice of the

charges 11.3.3. Aging and prevention products

11.3.4. Other adjuvants
11.4. Formulation realization: mixture

309 311
312

Filling factors of the machine 11.4.2. Monitoring the mixture

11.5. Conclusion 11.6.

11.4.1.

314 315
317

Bibliography

318 321
323

Conclusion

List of Authors Index

325