Drug Compounding for Veterinary Professionals

Lauren R. Eichstadt Forsythe, PharmD, DICVP, is a Clinical Assistant Professor and the Pharmacy Service Head at the University of Illinois Veterinary Teaching Hospital in Urbana, Illinois, USA.

Alexandria E. Gochenauer, PharmD, DICVP, is a clinical staff pharmacist at the University of Illinois Veterinary Teaching Hospital in Urbana, Illinois, USA.

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