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AAPS Introductions in the Pharmaceutical Sciences
Ashlee D. Brunaugh Daniel Moraga-Espinoza Tania F. Bahamondez-Canas Hugh D. C. Smyth Robert O. Williams
Essential Pharmaceutics
AAPS Introductions in the Pharmaceutical Sciences
Volume 12
Founding Editor
Robin Zavod, Chicago College of Pharmacy, Midwestern University, Downers Grove,IL,USA
Series Editor
ClaudioSalomon, National University of Rosario, Rosario,Argentina
The AAPS Introductions in the Pharmaceutical Sciences book series is designed to support pharmaceutical scientists at the point of knowledge transition. Springer and the American Association of Pharmaceutical Scientists (AAPS) have partnered again to produce a second series that juxtaposes the AAPS Advances in the Pharmaceutical Sciences series. Whether shifting between positions, business models, research project objectives, or at a crossroad in professional development, scientists need to retool to meet the needs of the new scientic challenges ahead of them. These educational pivot points require the learner to develop new vocabulary in order to effectively communicate across disciplines, appreciate historical evolution within the knowledge area with the aim of appreciating the current limitations and potential for growth, learn new skills and evaluation metrics so that project planning and subsequent evolution are evidence-based, as well as to simply “dust the rust off” content learned in previous educational or employment settings, or utilized during former scientic explorations. The Introductions book series will meet these needs and serve as a quick and easy-to-digest resource for contemporary science.
AshleeD.Brunaugh • DanielMoraga-Espinoza TaniaF.Bahamondez-Canas • HughD.C.Smyth RobertO.Williams
Essential Pharmaceutics
Second Edition
AshleeD.Brunaugh College of Pharmacy University of Michigan–Ann Arbor Ann Arbor, MI, USA
TaniaF.Bahamondez-Canas University of Valparaíso Valparaíso, Chile
RobertO.Williams College of Pharmacy The University of Texas at Austin Austin, TX, USA
DanielMoraga-Espinoza University of Valparaíso Valparaíso, Chile
HughD.C.Smyth College of Pharmacy The University of Texas at Austin Austin, TX, USA
ISSN 2522-834X ISSN 2522-8358 (electronic) AAPS Introductions in the Pharmaceutical Sciences ISBN 978-3-031-52519-3 ISBN 978-3-031-52520-9 (eBook)
https://doi.org/10.1007/978-3-031-52520-9
© American Association of Pharmaceutical Scientists 2019, 2024 Jointly published with American Association of Pharmaceutical ScientistsThis work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publishers, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publishers nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publishers remain neutral with regard to jurisdictional claims in published maps and institutional afliations.
Editorial Contact: Charlotte Nunes
This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Paper in this product is recyclable.

Contents

1 Essential Pharmaceutics in the Flipped Classroom . . . . . . . . . . . . . . . 1
1.1 Overview of “Flipped Pharmaceutics” Course Format
and Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Building the Required Foundation for Student Success
in “Flipped Pharmaceutics” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Achieving Learning Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.4 Specic “Flipped Class” Structure—How to Implement . . . . . . . . 8
1.5 Flipped Pharmaceutics—A Pathway to Success . . . . . . . . . . . . . . . 10
Further Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2 Overview of Biopharmaceutics and Regulatory Concepts
Relevant to Drug Product Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.2 Utilization of Pharmacokinetic Data to Determine
Bioavailability and Bioequivalence . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.3 Biopharmaceutics Classication System . . . . . . . . . . . . . . . . . . . . . 18
2.4 Overview of the Regulatory Pathways for Drug Product
Approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3 Preformulation in Drug Product Design . . . . . . . . . . . . . . . . . . . . . . . . 23
3.1 Introduction—Importance of Preformulation Studies
in Dosage Form Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2 Preformulation Studies—Factors Affecting Drug
Bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3.2.1 Solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
3.2.2 Dissociation Constant/pKa . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.2.3 Dissolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2.4 Partition Coefcient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2.5 Membrane Permeability . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.2.6 Biopharmaceutics Classication System (BCS) . . . . . . . . . 32
3.3 Preformulation Studies—Solid-State Characterization . . . . . . . . . . 32
v
vi
Contents
3.3.1 Organoleptic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.3.2 Amorphous and Crystalline Morphologies . . . . . . . . . . . . . 33
3.3.3 Particle and Powder Characteristics . . . . . . . . . . . . . . . . . . . 38
3.3.4 Particle Size and Distribution . . . . . . . . . . . . . . . . . . . . . . . 39
3.4 Formulation Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.4.1 Degradation by Hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.4.2 Degradation by Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.4.3 pH-Dependent Degradation . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.4.4 Degradation by Photolysis . . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.4.5 Hygroscopicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
3.4.6 Epimerization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3.4.7 Arrhenius Equation and Kinetics . . . . . . . . . . . . . . . . . . . . . 44
3.5 Other Considerations in Preformulation Studies . . . . . . . . . . . . . . . 45
3.5.1 Prodrugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.5.2 Stereoisomers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4 Capsule and Tablet Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2 Capsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2.1 Hard Shell Capsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.2.2 Soft Gel Capsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
4.3 Tablets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
4.3.1 Manufacturing Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.4 Excipients Utilized in Capsules and Tablets . . . . . . . . . . . . . . . . . . 59
4.5 Analytical Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
4.5.1 Disintegration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
4.5.2 Dissolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
4.5.3 Weight Variation and Dose Content Uniformity . . . . . . . . . 64
4.5.4 Tablet Hardness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
4.5.5 Friability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
4.6 Formulating Poorly Water-Soluble Drugs . . . . . . . . . . . . . . . . . . . . 66
4.6.1 Spring and Parachute Concept . . . . . . . . . . . . . . . . . . . . . . . 67
4.6.2 Hot Melt Extrusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
4.6.3 Spray Drying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
4.7 Physiology and Food Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
5 Modified Release Solid Oral Dosage Forms . . . . . . . . . . . . . . . . . . . . . 73
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
5.2 Delayed Release Solid Oral Dosage Forms . . . . . . . . . . . . . . . . . . . 75
5.3 Extended Release Solid Oral Dosage Forms . . . . . . . . . . . . . . . . . . 77
5.3.1 Hydrophilic Matrix Drug Delivery Systems . . . . . . . . . . . . 79
5.3.2 Insoluble Matrix Systems . . . . . . . . . . . . . . . . . . . . . . . . . . 81
5.3.3 Membrane-Controlled Release Systems . . . . . . . . . . . . . . . 81
5.3.4 Osmotic Pump Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
5.3.5 Compression Coating Systems . . . . . . . . . . . . . . . . . . . . . . 84
Contents
vii
5.4 Pulsatile Release Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
5.5 USP Dissolution Testing for Modied-Release Dosage Forms . . . . 86
5.6 Dose Dumping and Alcohol Effects. . . . . . . . . . . . . . . . . . . . . . . . . 87
5.7 Abuse-Deterrent Technologies for Extended Release Opioid
Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Further Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
6 Solution-Based Dosage Forms and Sterile Products . . . . . . . . . . . . . . 91
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
6.2 Drug Solubility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
6.2.1 Factors Inuencing Solubility . . . . . . . . . . . . . . . . . . . . . . . 94
6.2.2 Factors Inuencing Dissolution . . . . . . . . . . . . . . . . . . . . . . 95
6.3 Excipients for Pharmaceutical Preparations . . . . . . . . . . . . . . . . . . 96
6.3.1 Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
6.3.2 Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
6.3.3 Chelating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
6.3.4 Preservatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
6.3.5 Complexing Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.3.6 Surfactants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
6.4 Parenteral Route of Administration and Injectable Dosage
Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.4.1 Routes of Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.4.2 Isotonicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.4.3 pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.4.4 Syringeability and Injectability . . . . . . . . . . . . . . . . . . . . . . 103
6.4.5 Long-Acting Injectable Formulations . . . . . . . . . . . . . . . . . 104
6.5 Lyophilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
6.6 Sterilization of Pharmaceutical Products . . . . . . . . . . . . . . . . . . . . . 105
6.6.1 Heat Sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
6.6.2 Sterilization of Heat-Sensitive Drugs . . . . . . . . . . . . . . . . . 106
6.6.3 Pyrogen Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
6.7 Packaging of Sterile Injections . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
6.7.1 Labeling Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
7 Disperse Systems: Suspensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
7.2 Properties of Suspensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.2.1 Particle Settling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.2.2 Flocculation, Deocculation, and Aggregation . . . . . . . . . . 113
7.2.3 Rheology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
7.2.4 Electrical Charge and Zeta Potential . . . . . . . . . . . . . . . . . . 115
7.3 Stability of Suspensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
7.3.1 Particle Settling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
7.3.2 Particle Aggregation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
7.3.3 Particle Growth (Ostwald Ripening) . . . . . . . . . . . . . . . . . . 117
viii
Contents
7.4 Methods of Particle Size Reduction for Suspensions . . . . . . . . . . . 118
7.5 Colloidal Dispersions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
7.5.1 Light Scattering Properties of Colloids . . . . . . . . . . . . . . . . 119
7.5.2 Kinetic Movement of Colloids . . . . . . . . . . . . . . . . . . . . . . . 119
7.5.3 Nanoparticles in Suspensions . . . . . . . . . . . . . . . . . . . . . . . 120
7.6 Excipients Used in Suspension Formulations . . . . . . . . . . . . . . . . . 122
7.6.1 Suspending Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
7.6.2 Surfactants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
7.6.3 Flocculating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
7.6.4 Sweetening Agents and Flavors . . . . . . . . . . . . . . . . . . . . . . 127
7.6.5 Other Excipients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
7.7 Sterility and Sterilization of Dispersed Systems . . . . . . . . . . . . . . . 128
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
8 Disperse Systems: Emulsions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
8.2 Emulsion Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
8.3 Routes of Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.3.1 Oral Route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.3.2 Topical Route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.4 Emulsifying Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.4.1 Stabilization Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
8.4.2 Hydrophile-Lipophile Balance. . . . . . . . . . . . . . . . . . . . . . . 135
8.4.3 Types of Emulsifying Agents . . . . . . . . . . . . . . . . . . . . . . . . 136
8.5 Other Excipients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
8.6 Preparation of Emulsions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
8.7 Colloidal Dispersions—Microemulsions . . . . . . . . . . . . . . . . . . . . . 138
8.7.1 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
8.8 Emulsion Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
8.8.1 Aggregation and Coalescence . . . . . . . . . . . . . . . . . . . . . . . 139
8.8.2 Phase Separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
8.8.3 Phase Inversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
9 Ophthalmic and Otic Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
9.2 Special Considerations in Ophthalmic Dosage Forms . . . . . . . . . . . 143
9.2.1 Sterility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.2.2 Tonicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.2.3 pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.2.4 Ocular Bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
9.2.5 Packaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
9.2.6 Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
9.3 Types of Ophthalmic Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . 146
9.4 Special Considerations in Otic Dosage Forms . . . . . . . . . . . . . . . . . 148
9.5 Types of Otic Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Contents
10 Topical and Transdermal Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . 151
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
10.2 Anatomy of the Skin—A Brief Review . . . . . . . . . . . . . . . . . . . . . 153
10.3 Diffusion of Drug Through the Skin . . . . . . . . . . . . . . . . . . . . . . . 154
10.3.1 Application of Fick’s Law of Diffusion . . . . . . . . . . . . . . . 154
10.3.2 Transport Through the Skin Layers . . . . . . . . . . . . . . . . . . 155
10.3.3 In Vitro Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
10.4 Mechanisms of Enhancing Drug Penetration Through Skin . . . . . 157
10.4.1 Diffusion Coefcient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
10.4.2 Partition Coefcient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
10.4.3 Degree of Drug Saturation in the Formulation . . . . . . . . . 159
10.4.4 Electrical and Mechanical Methods of Increasing
Drug Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
10.5 Topical Semi-Solid Formulations . . . . . . . . . . . . . . . . . . . . . . . . . 160
10.5.1 Ointment Bases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
10.5.2 Ointment Manufacture/Preparation . . . . . . . . . . . . . . . . . . 162
10.5.3 Gels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
10.6 Transdermal Patches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
10.6.1 Patch Design, Formulation, and Manufacture . . . . . . . . . . 164
10.6.2 Drug Release from Transdermal Patches . . . . . . . . . . . . . . 165
10.6.3 Patient Counseling—Transdermal Systems . . . . . . . . . . . . 166
10.7 Additional Excipients Utilized in Topical and Transdermal
Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
ix
11 Oral Transmucosal Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
11.2 Barriers for Oral Mucosal Drug Delivery . . . . . . . . . . . . . . . . . . . 173
11.2.1 Oral Mucosal Membrane Barriers . . . . . . . . . . . . . . . . . . . 173
11.2.2 Residence Time and Dilution . . . . . . . . . . . . . . . . . . . . . . . 174
11.2.3 Other Barriers and Considerations . . . . . . . . . . . . . . . . . . . 174
11.3 Methods of Oral Transmucosal Administration . . . . . . . . . . . . . . . 175
11.3.1 Tablets, Lozenges, and Troches . . . . . . . . . . . . . . . . . . . . . 175
11.3.2 Films and Patches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
11.3.3 Other Oral Transmucosal Dosage Forms . . . . . . . . . . . . . . 176
11.4 Excipients Used in Oral Transmucosal Formulations . . . . . . . . . . 177
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
12 Rectal and Vaginal Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
12.2 Rectal Route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
12.2.1 Rectum Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
12.2.2 Rectal Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
12.3 Vaginal Route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
12.3.1 Vaginal Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
12.3.2 Vaginal Dosage Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186