Pharmaceutical Emulsions: A Drug Developers Toolbag

Pharmaceutical Emulsions: A Drug Developer’s Toolbag covers all the key aspects of pharmaceutical emulsions, starting from the fundamental scientific basics, to the pharmaceutical forms and the chemical tests for their application. The author uses his extensive experience in both industry and academia to provide a concise, student–friendly guide to the essential fundamentals of physical pharmacy. Emulsions are explained in terms of their stability, instability and manufacture. Descriptions are provided for a whole variety of forms, from creams and ointments to pastes and bases, colloids, gels and implants. Finally tests that are used to control the quality, efficacy and safety of preparations are included; ranging from physical–chemical properties to sizing and microscopy, rheology, and quality control. • Provides students and those in industry with a concise and student–friendly guide   to the essential fundamentals in physical pharmacy • Includes key aspects of pharmaceutical emulsions including scientific basics,   pharmaceutical forms and the chemical tests for their application • Highly–regarded author with both industry and academic experience • Specimen case studies, ‘test’ questions and MCQs are included • Companion website with further case studies This is an invaluable reference for all students of pharmaceutical sciences, pharmacy industrial pharmaceutical sciences, physical pharmacy and pharmaceutical forms. It will also appeal to industry professionals.

Mathematical symbols (with normal units) xi Acronyms and abbreviations xiii Preface xv Acknowledgements xvii About the companion website xix I Product considerations: medicinal formulations 1 1 Historical perspective 5 1.1 Landmarks 5 1.2 Significant discoveries 7 1.3 Difficulties 8 1.4 Traditional uses 10 1.5 Product regulation 13 2 What is an emulsion? 15 2.1 States of matter 24 2.2 Summary thermodynamics 34 2.3 Interfacial tension and wetting 36 2.4 Shear and size reduction 46 2.5 Raw materials 47 3 Stability, metastability and instability 49 3.1 Stokes’ law 51 3.2 Derjaguin–Landau–Verwey–Overbeek (DLVO) theory 52 3.3 Interfacial rheology 56 4 Manufacture 63 4.1 Premixing 63 4.2 High–shear mixers and size reduction 64 4.3 Multiple and microemulsions 65 4.4 Hot melt (steriles) 65 4.5 Filling 66 II Forms, uses and applications: biopharmaceutics 67 5 Creams and ointments 69 5.1 Nutraceuticals and cosmeceuticals 71 5.2 Medicinals 71 6 Pastes and bases 77 6.1 Emolliency 77 6.2 Suppositories 78 6.3 Pessaries 79 7 IV colloids 81 7.1 Needle free 86 7.2 Ocular therapy 87 7.3 Cancer 88 7.4 Antimicrobials 90 7.5 Temperature–sensitive matrices and release forms 93 7.6 Targeted endosomal use 94 7.7 Solid lipid nanoparticles 95 7.8 Diagnostic emulsions 98 8 Transdermal patches: semisolids 99 8.1 Hormones 104 8.2 Analgesia 104 8.3 Anaesthesia 104 8.4 Nicotine 105 8.5 Inserts: vaginal rings 105 9 Gels 107 9.1 Micro– and nanogels 107 9.2 Semisolids 107 10 Implants 109 10.1 Plastics and glasses 109 10.2 Thermoresponsive materials 110 11 De novo science, sustainable novel products and platform applications 111 11.1 Tablets 113 11.2 Metered–dose inhalers 113 11.3 Blood substitutes 114 III Tests: chemistry to control the quality, efficacy and fitness for purpose of a product 117 12 Physicochemical properties 119 12.1 Thermal evaluation (differential scanning calorimetry) and lipid polymorphs 124 12.2 Drug form, log P and Lipinski rules 129 12.3 Skin and epithelial models 133 12.4 Drug delivery routes 134 13 Sizing and microscopy 137 13.1 ζ –potential 137 13.2 Hydrodynamic diameter 139 14 Rheology, texture, consistency and spreadability 141 14.1 Bulk properties 141 14.2 Solid–state and nanorheological properties 144 14.3 Interfacial properties 144 15 Quality control, process analytical technology and accelerated testing 149 15.1 Preformulation, high–throughput screening 150 15.2 Industrial concerns 151 15.3 Rancimat and other methods 152 Questions 155 Guide for readers 155 Specimen ‘test’ questions 155 Answers 168 References 173 Index 181

Dipak K. Sarker School of Pharmacy and Biomolecular Sciences, University of Brighton, UK