Handbook of Pharmaceutical Manufacturing Formulations, Third Edition-Volume Five, Over-the-Counter Products

453 Pages·2019·6.377 MB·\453

by  Sarfaraz K. Niazi (Author)

Handbook of Pharmaceutical
Manufacturing Formulations
Volume Five, Over-the-Counter Products

Handbook of Pharmaceutical
Manufacturing Formulations,
Third Edition
Volume Five, Over-the-Counter Products
Sarfaraz K. Niazi
CRC Press
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Contents
Preface to the Series—Third Edition .........................................................................................................................................xxi
Preface to the Series—Second Edition ....................................................................................................................................xxiii
Preface to the Series—First Edition .......................................................................................................................................xxvii
Preface to the Volume—First Edition......................................................................................................................................xxix
Author ...................................................................................................................................................................................xxxiii
PART I Regulatory Guidance
Chapter 1 European Directorate for the Quality of Medicines (EDQM) Certification ...........................................................3
1.2.3.S Drug Substance ........................................................................................................................................4
A.2.3.S.1 General Information ..............................................................................................................4
1.2.3.S.1.1 Nomenclature ...................................................................................................4
1.2.3.S.1.2 General Properties ............................................................................................4
2.3.S.2 Manufacture .............................................................................................................................................4
2.3.S.2.1 Manufacturer(s) (Name, Manufacturer) and Sites Involved in the Entire Process ................4
2.3.S.2.2 Description of Manufacturing Process and Process Controls ................................................4
2.3.S.2.3 Control of Materials ...............................................................................................................4
2.3.S.2.4 Controls of Critical Steps and Intermediates .........................................................................4
2.3.S.2.5 Process Validation and/or Evaluation .....................................................................................4
2.3.S.3 Characterization .......................................................................................................................................4
2.3.S.3.1 Impurities ...............................................................................................................................4
2.3.S.4 Control of the Drug Substance .................................................................................................................5
2.3.S.4.1 Specification ...........................................................................................................................5
2.3.S.4.2 Analytical Procedures ............................................................................................................5
2.3.S.4.3 Validation of Analytical Procedures .......................................................................................5
2.3.S.4.4 Batch Analyses .......................................................................................................................5
2.3.S.4.5 Justification of Specification ..................................................................................................5
2.3.S.5 R eference Standards or Materials ............................................................................................................5
2.3.S.6 Container Closure System ........................................................................................................................5
2.3.S.7 S tability ....................................................................................................................................................5
2.3.S.7.1 Stability Summary and Conclusions ......................................................................................5
2.3.S.7.2 Postapproval Stability Protocol and Stability Commitment ..................................................5
Chapter 2 Solid Oral Dosage Forms Validation ......................................................................................................................7
I. Introduction ..................................................................................................................................................7
II. Background ...................................................................................................................................................7
III. Product Development ...................................................................................................................................7
A. Product Development Reports ..............................................................................................................7
1. Drug Substance Characterization ..................................................................................................8
2. Manufacturing Procedures ............................................................................................................9
3. In-Process Testing .........................................................................................................................9
4. Finished Product Testing ..............................................................................................................9
5. Dissolution Profile .........................................................................................................................9
6. Stability .........................................................................................................................................9
B. P reapproval Inspections ........................................................................................................................9
1. Master Formula .............................................................................................................................9
2. History Section of the Application ................................................................................................9
3. Development Data (Product Development Report) ......................................................................9
4. Inspection of the Facilities ..........................................................................................................10
5. Raw Materials .............................................................................................................................10
vii
viii Contents
6. Laboratory ...................................................................................................................................10
7. Equipment ...................................................................................................................................10
IV. Validation Protocols ...................................................................................................................................10
V. Demonstration Runs (Validation Of The Process) .....................................................................................10
A. Test Batch Relationships ....................................................................................................................10
B. Postapproval Prospective Validation Inspections ...............................................................................10
1. Raw Materials .............................................................................................................................11
2. Manufacturing Procedures and Equipment .................................................................................11
3. Granulation/Mix Analysis ...........................................................................................................13
4. In-Process Testing .......................................................................................................................14
5. Test Results .................................................................................................................................14
6. Investigations and Product Failures ............................................................................................14
7. Site Review .................................................................................................................................15
Chapter 3 Current Regulatory Status of Over-the-Counter Products ....................................................................................17
Background ...........................................................................................................................................................17
Regulatory Definitions ..........................................................................................................................................17
Appendix I OTC Ingredient List ...........................................................................................................................19
Appendix II Unproven Safety of OTC Ingredients .............................................................................................106
Chapter 4 Bioequivalence of Complementary and Alternative Medicines ..........................................................................117
Background ..........................................................................................................................................................117
Appendix A: GMP Audit Template .......................................................................................................................................121
Appendix B: OTC Process and Ingredients ..........................................................................................................................143
PART II Manufacturing Formulations
Over-the-Counter Formulations ............................................................................................................................................197
Acetaminophen and Caffeine Tablets .................................................................................................................197
Acetaminophen and Caffeine Tablets .................................................................................................................197
Acetaminophen and Diphenhydramine Hydrochloride Hot Therapy Sachets ....................................................198
Acetaminophen and Pseudoephedrine Hydrochloride Hot Therapy Sachets .....................................................198
Acetaminophen and Diphenhydramine Hydrochloride Tablets ..........................................................................198
Acetaminophen Sustained-Release Tablets .........................................................................................................199
Acetaminophen and Pseudoephedrine Hydrochloride Tablets ...........................................................................199
Acetaminophen Chewable Tablets ......................................................................................................................200
Acetaminophen, Chlorpheniramine, and Pseudoephedrine Syrup .....................................................................200
Acetaminophen, Chlorpheniramine Maleate, and Pseudoephedrine Caplets ....................................................201
Acetaminophen, Dextromethorphan, and Pseudoephedrine Caplets ..................................................................202
Acetaminophen, Doxylamine, and Caffeine Effervescent Granules ..................................................................202
Acetaminophen Drops .........................................................................................................................................202
Acetaminophen Effervescent Tablets ..................................................................................................................203
Acetaminophen Fast-Dissolving Tablets .............................................................................................................203
Acetaminophen, Ibuprofen, and Orphenadrine Hydrochloride Tablets ..............................................................203
Acetaminophen Instant Granules ........................................................................................................................203
Acetaminophen Instant Granules ........................................................................................................................204
Acetaminophen Instant Granules ........................................................................................................................204
Acetaminophen Microsphere Tablets ..................................................................................................................204
Acetaminophen, Norephedrine, and Phenyltoloxamine Tablets .........................................................................205
Acetaminophen Oral Suspension ........................................................................................................................205
Acetaminophen, Phenylpropanolamine, Dextromethorphan, and Chlorpheniramine Tablets ...........................206
Acetaminophen, Propoxyphenazone, and Caffeine Tablets................................................................................206
Acetaminophen, Pseudoephedrine Hydrochloride, and Chlorpheniramine Hot Therapy Sachet ......................207
Contents ix
Acetaminophen Suppositories .............................................................................................................................207
Acetaminophen Suppositories .............................................................................................................................207
Acetaminophen Suppositories .............................................................................................................................207
Acetaminophen Suppositories .............................................................................................................................208
Acetaminophen Suppositories .............................................................................................................................208
Acetaminophen Suspension ................................................................................................................................208
Acetaminophen Syrup .........................................................................................................................................208
Acetaminophen Syrup .........................................................................................................................................209
Acetaminophen Syrup for Children ....................................................................................................................209
Acetaminophen Tablets .......................................................................................................................................209
Acetaminophen Tablets ........................................................................................................................................210
Acetaminophen Tablets ........................................................................................................................................210
Acetaminophen Tablets ........................................................................................................................................210
Acetaminophen Tablets for Children ...................................................................................................................210
Acetylcysteine Sachets .........................................................................................................................................211
Acetylsalicylic Acid, Acetaminophen, and Caffeine Tablets (250 mg + 250 mg + 50 mg) ................................211
Acetylsalicylic Acid + Paracetamol (=Acetaminophen) Tablets (250 mg + 250 mg) ..........................................211
Acetylsalicylic Acid + Vitamin C Tablets (400 mg + 250 mg) ...........................................................................212
Acetylsalicylic Acid Tablets (500 mg) ................................................................................................................212
Acetylsalicylic Acid, Acetaminophen, and Caffeine Tablets ..............................................................................212
Acetylsalicylic Acid, Acetaminophen, and Caffeine Tablets (Direct Compression) ..........................................212
Acetylsalicylic Acid and Acetaminophen Tablets ...............................................................................................212
Acetylsalicylic Acid and Acetaminophen Tablets ...............................................................................................213
Acetylsalicylic Acid and Ascorbic Acid Tablets .................................................................................................213
Acetylsalicylic Acid and Ascorbic Acid Tablets .................................................................................................213
Acetylsalicylic Acid Suppositories ......................................................................................................................213
Acetylsalicylic Acid Tablets (Buffered) ...............................................................................................................214
Acetylsalicylic Acid Tablets (Direct Compression) .............................................................................................214
Acetylsalicylic Acid Tablets (Direct Compression) .............................................................................................214
Acetylsalicylic Acid Tablets (Direct Compression) .............................................................................................214
Acne Cover Cream ..............................................................................................................................................215
Acne Scrub ..........................................................................................................................................................215
Acne Treatment Cream .......................................................................................................................................215
Alginic Acid + Aluminum Hydroxide + Magnesium Silicate Tablets (500 mg+100 mg+25 mg) ......................215
Aloe Vera Gel .......................................................................................................................................................216
Alpha-Bisabolol Aqueous Mouthwash Solution ...................................................................................................216
Alpha-Bisabolol Buccal or Topical Solution ........................................................................................................216
Alpha-Bisabolol Ethanolic Mouthwash Solution .................................................................................................216
Alpha-Bisabolol Mouthwash Solution ..................................................................................................................216
Aluminum Acetylsalicylate Tablets .....................................................................................................................217
Aluminum Hydroxide + Magnesium Silicate Chewable Tablets (120 mg+250 mg) ............................................217
Aluminum Hydroxide and Magnesium Carbonate Dry Syrup ............................................................................217
Aluminum Hydroxide and Magnesium Hydroxide Chewable Tablets .................................................................217
Aluminum Hydroxide and Magnesium Hydroxide Chewable Tablets .................................................................218
Aluminum Hydroxide and Magnesium Hydroxide Antacid Suspension .............................................................218
Aluminum Hydroxide and Magnesium Hydroxide Antacid Suspension .............................................................218
Aluminum Hydroxide and Magnesium Hydroxide Suspension ...........................................................................218
Aluminum Hydroxide and Magnesium Hydroxide Suspension ...........................................................................219
Aluminum Hydroxide and Magnesium Hydroxide Suspension ...........................................................................219
Aluminum Hydroxide and Magnesium Hydroxide Tablets ................................................................................220
Aluminum Hydroxide and Magnesium Silicate Chewable Tablets.....................................................................220
Aluminum Hydroxide, Magnesium Carbonate (or Oxide), and Simethicone Tablets ........................................220
Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension ...................................................221
Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension ...................................................221
Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Tablets .........................................................221
Analgesic Clear Gel ............................................................................................................................................222
Analgesic Cream .................................................................................................................................................222