Drug Compounding for Veterinary Professionals

Foreword xi Preface xiii List of Acronyms xiv About the Companion Website xvi Introduction xvii 1 Compounding Regulations 1 Organizations and Regulatory Agencies Involved with Compounding 3 Food and Drug Administration 3 United States Pharmacopeia 3 Drug Enforcement Administration 5 State Boards of Pharmacy 6 State Veterinary Boards 6 Compliance Policy Guides and Guidance for Industry Documents 6 What Is Compounding? 7 The Food, Drug, and Cosmetic Act 9 Animal Medicinal Drug Use Clarification Act 9 Preparing Compounds from an Approved Product or a Pure Drug Powder 10 Federal Versus State Law 11 Office Use Compounding 12 Drug Quality and Security Act 13 Finding Additional Information 13 2 Risk–Benefit Analysis of Compounded Medications 17 Benefits of Compounded Products 17 Dosage Form 17 Flavoring 20 Dosage Strength 20 Eliminating Ingredients 21 Availability Issues 22 Appropriate Use of Compounded Medications 22 FDA-Approved Drugs 23 Compounded Medication Risks 25 Compounded (USP) Versus Manufactured (cGMP) 26 Risks Associated with Compounded Medications – A Look at the Literature 28 Studies Showing Incorrect Potency 28 Studies Showing Lack of Stability 31 Studies Showing Lack of Efficacy 31 Risks Associated with Specific Types of Compounds 32 Active Ingredient Source Decisions 34 Patient-Specific Compounding Versus Office Use Compounding 35 Adverse Event Reporting 36 Identifying Potential Formulation Issues 37 Drug Recalls 38 Selecting a Compounding Pharmacy 39 Client Education 40 Reducing Risk in Practice 40 Conclusion 41 3 Beyond-Use Dating 45 Factors Considered When Assigning BUDs and Expiration Dates 45 USP Default BUDs 48 Stability Studies 49 Evaluating Stability Studies 50 Determining BUDs for In-House Formulations 51 BUD Considerations When Prescribing Compounded Medications 52 Conclusion 53 4 Identifying High-Quality Compounding Pharmacies 55 Case Study 1 55 Case Study 2 58 What to Evaluate 59 General Practices 59 Staff Skill Level 61 Familiarity with Veterinary Medicine 61 Pharmacy Culture 61 Ways to Evaluate Compounding Pharmacies 62 Looking Beyond the Pharmacy’s Website 63 What to Look for on a Tour 65 Questions to Ask the Pharmacist in Charge 65 Conclusion 67 5 Formulation Development 69 Dosage Forms 69 Oral Administration 69 Oral Solutions 69 Oral Suspensions 70 Oral Syrups 70 Oral Capsules 71 Oral Tablets 72 Oral Treats 73 Oral Emulsions 73 Oral Pastes 74 Oral Powders 74 Transdermal Administration 74 Topical Administration 75 Topical Solutions 75 Topical Ointments 76 Topical Shampoos 76 Topical Mousses 76 Topical Emulsions 76 Topical Creams 77 Topical Gels 77 Otic Administration 77 Otic Solutions 77 Otic Suspensions 77 Otic Ointments 78 Other Routes of Administration 78 Rectal Solutions 78 Intranasal Solutions 78 Injectable Preparations 78 Ophthalmic Preparations 79 Ingredients 79 Ingredient Selection 79 Solubility 81 Partition Coefficient 82 Density 83 Water Activity 83 pH 83 Chelators 84 Antioxidants 84 Preservatives 84 Flavors, Coating Agents, and Sweeteners 85 Coloring Agents 87 Salt Forms 87 Organic Salts 88 Inorganic Salts 88 Common Excipients by Dosage Form 89 Oral Liquid Medications 89 Oral Solid Medications 89 Emulsions 91 Transdermal Medications 91 Cream, Gel, and Ointment Medications 91 Hazardous Drugs 92 Beyond-Use Dates 92 Formulation Resources 93 Calculations 93 Measurements Used in Compounding 96 Displacement Factor 96 Capsules: Packing Statistics 98 Packing Statistic of Drug 98 Average Weight of Ingredients 98 Percentage of Drug per Capsule Using Bulk Powder 98 Percentage of Drug per Capsule Using Manufactured Tablets 99 Percentage/Amount of Filler per Capsule 101 Conversion to Grams 101 Compounding Formulations to Avoid 102 Formulation Development Process 103 Developing a Compounding Formula: Example 1 (USP Compounding Compendium) 104 Developing a Compounding Formula: Example 2 (Stability-Indicating Assay) 106 Compounding Formulation Assessment 108 6 Compounding in House 111 Documentation 111 Master Formulation Record 111 Compounding Record 111 Formulation Record Components 112 Quality Assurance and Quality Control 116 Labeling 118 Packaging and Storage 119 Compounding Techniques 120 Trituration 120 Sifting 121 Geometric Dilution 121 Wetting 121 Colored Tracers 122 Equipment 122 Mortars and Pestles 124 Glassware 125 Containers 125 Scales 127 Spatulas and Measuring Devices 129 Equipment Cleaning 129 Training 130 Formulation Instructions 132 Species-Specific Information 135 Flavoring 135 Toxicities 136 Potency Designations 138 Feasibility for a Veterinary Clinic 139 Index 141