H A N D B O O K O F

PharmaceuticalManufacturingFormulationsOver-the-Counter Products

VOLUME 5

Sarfaraz K. Niazi

CRC PRESSR . n o n I n M i l i i i i N V \ \ V > i k \ \ . i - . l i n n ; i < H I . I V l

Table of Contents

PartiRegulatory Guidance.

Chapter 1Good Manufacturing Practices in Over-the-Counter Drug Product Manufacturing 3I. Introduction 3II. Buildings and Facilities (21 CFR 211, Subpart C) 3III. Equipment (21 CFR 211, Subpart D) 3IV. Components and Product Containers (21 CFR 211, Subpart E) 4V. Production and Process Controls (21 CFR 211, Subpart F) 4

A. Critical Manufacturing Steps (21 CFR 211.101) 4B. Equipment Identification (21 CFR 211.105) 5C. In-Line and Bulk Testing (21 CFR 211.110) 5D. Actual Yield (21 CFR 211.103) 5E. Personnel Habits 5F. Tablet and Capsule Products 5G. Sterile Products 5

1. Personnel 62. Buildings A3. Air 64. Environmental Controls 65. Equipment 66. Water for Injection 67. Containers and Closures 6

H. Sterilization 61. Methods 62. Indicators 73. Filled Containers 74. Personnel Practices 8

I. Laboratory Controls 81. Retesting for Sterility 82. Retesting for Pyrogens 83. Paniculate Matter Testing 8

J. Production Records 8K. Ointments, Liquids, and Lotions 8

VI. Packaging and Labeling (21 CFR. Subpart G) SVII. Holding and Distribution (21 CFR, Subpart H) 10VIII. Laboratory Controls (21 C F R . Subpart I) 10

A. Sterility Testing Procedures 10IX. Control Records (21 CFR 2 1 1 , Subpart J) I 1

A. Master Production and Control Records (21 CFR 21 1.186) 1 |B. Batch Production and Control Records (21 CFR 21 1.188) I I

C. Distribution (21 CFR 2 1 1 . 1 % ) I 1D. Compla in t Files (21 C F R 211.198) I 1

X. Returned Drug Products (21 CFR 211, Subpart K) 11Appendix 12

1 Personnel 122 Hygiene 123 Warehouse 134 Dispensing/Assembling 155 Solids Manufacturing 156 Liquids Manufacturing 187 Packaging 238 Documentation 259 Quality Control 28

10 Complaints and Product Recalls 3111 Self Inspection 3112 Contract Manufacture and Analysis 3213 Audit of Suppliers 33

Chapter 2Solid Oral Dosage Forms 35I. Introduction 35II. Background 35III. Product Development 35

A. Product Development Reports 351. Drug Substance Characterization 362. Manufacturing Procedures 373. In-Process Testing 374. Finished Product Testing 375. Dissolution Profile 376. Stability 37

B. Pre-Approval Inspections 371. Master Formula 382. History Section of the Application 383. Development Data (Product Development Report) 384. Inspection of the Facilities 385. Raw Materials 386. Laboratory 387. Equipment 39

IV. Validation Protocols 39V. Demonstration Runs (Validation of the Process) 39

A. Test Batch Relationships 39B. Post-Approval Prospective Validation Inspections 39

1. Raw Materials 392. Manufacturing Procedures and Equipment 393. Granulation/Mix Analysis 424. In-Process Testing 435. Test Results 436. Investigations and Product Failures 437. Site Review 44

Chapter 3Oral Solutions and Suspensions 45I. Introduction 45II. Facilities 45III. Equipment 45IV. Raw Materials 45

V. Compounding 46VI. Microbiological Quality 46VII. Oral Suspension Uniformity 46VIII. Product Specifications 47IX. Process Validation 47X. Stability 47XI. Packaging 47

Chapter 4Validation of Cleaning Process 49I. Introduction 49II. Background 49III. General Requirements 49IV. Evaluation of Cleaning Validation 50

A. Equipment Design 50B. Cleaning Process, Written Procedure, and Documentation 51C. Analytical Methods 51D. Sampling 51

1. Direct Surface Sampling 512. Rinse Samples 513. Routine Production In-Process Control Monitoring 51

V. Establishment of Limits 51VI. Other Issues 52

A. Placebo Product 52B. Detergent 52C. Test Until Clean 52

Part IIOver-the-Counter Product Formulations 53Acetaminophen and Caffeine Tablets 55Acetaminophen and Caffeine Tablets 55Acetaminophen and Diphenhydramine Hydrochloride Hot Therapy Sachets 56Acetaminophen and Pseudoephedrine Hydrochloride Hot Therapy Sachets 56Acetaminophen and Diphenhydramine Hydrochloride Tablets 57Acetaminophen and Pseudoephedrine Hydrochloride Tablets 58Acetaminophen Chewable Tablets 58Acetaminophen, Chlorpheniramine. and Pseudoephedrine Syrup 59Acetaminophen, Chlorpheniramine Maleate, and Pseudoephedrine Caplets 60Acetaminophen, Dextromethorphan. and Pseudoephedrine Caplets 61Acetaminophen. Doxylamine. and Caffeine Effervescent Granules 61

Acetaminophen Drops 62Acetaminophen Effervescent Tablets 62Acetaminophen. Ibuprofen. and Orphenadine Hydrochloride Tablets 63Acetaminophen Instant Granules 63Acetaminophen Instant Granules 64Acetaminophen Instant Granules 64Acetaminophen. Norephedrine. and Phenylloloxamine Tablets d.SAcetaminophen Oral Suspension 66Acetaminophen, Phenylpropanoloainine. Dextromethorphan. and Chlorpheniramine Tablets 67Acetaminophen, Propoxyphenazone. and Caffeine Tablets (,SAcetaminophen, Pseudoephedrine Hydrochloride. and Chlorpheniramine Hot Therap\ Sachet 69Acetaminophen Suppositories WAcetaminophen Suppositories 69

Acetaminophen Suppositories 70Acetaminophen Suppositories 70Acetaminophen Suppositories 70Acetaminophen Suspension 71Acetaminophen Syrup 71Acetaminophen Syrup 72Acetaminophen Syrup for Children 72Acetaminophen Tablets 73Acetaminophen Tablets 73Acetaminophen Tablets 74Acetaminophen Tablets 74Acetaminophen Tablets for Children 74Acetylcysteine Sachets 75Acetylsalicylic Acid, Acetaminophen, and Caffeine Tablets 75Acetylsalicylic Acid, Acetaminophen, and Caffeine Tablets (Direct Compression) 76Acetylsalicylic Acid and Acetaminophen Tablets 76Acetylsalicylic Acid and Acetaminophen Tablets 76Acetylsalicylic Acid and Ascorbic Acid Tablets 77Acetylsalicylic Acid and Ascorbic Acid Tablets 77Acetylsalicylic Acid Suppositories 77Acetylsalicylic Acid Tablets, Buffered 78Acetylsalicylic Acid Tablets (Direct Compression) 78Acetylsalicylic Acid Tablets (Direct Compression) 79Acetylsalicylic Acid Tablets (Direct Compression) 79Acne Cover Cream 80Acne Scrub 80Acne Treatment Cream 81Aloe Vera Gel 81alpha-Bisabolol Aqueous Mouthwash Solution 82alpha-Bisabolol Buccal or Topical Solution 82alpha-Bisabolol Ethanolic Mouthwash Solution 82alpha-Bisabolol Mouthwash Solution 83Aluminum Hydroxide and Magnesium Carbonate Dry Syrup 83Aluminum Acetylsalicylate Tablets 84Aluminum Hydroxide and Magnesium Hydroxide Chewable Tablets 84Aluminum Hydroxide and Magnesium Hydroxide Chewable Tablets 85Aluminum Hydroxide and Magnesium Hydroxide Antacid Suspension 85Aluminum Hydroxide and Magnesium Hydroxide Antacid Suspension 86Aluminum Hydroxide and Magnesium Hydroxide Suspension 87Aluminum Hydroxide and Magnesium Hydroxide Suspension 88Aluminum Hydroxide and Magnesium Hydroxide Suspension 88Aluminum Hydroxide and Magnesium Hydroxide Tablets 89Aluminum Hydroxide and Magnesium Silicate Chewable Tablets 89Aluminum Hydroxide, Magnesium Carbonate (or Oxide), and Simethicone Tablets 90Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension 90Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension 91Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Tablets 92Analgesic Clear Gel 93Analgesic Cream 93Analgesic Lotion 94Anise Oil Solution 94Antazoline and Xylometazoline Eye Drops 95Anti-Acne Gel 95Antifungal Foot Powder 96Antiseptic Cream 96

Antiseptic Lotion 96Antiseptic Lotion 97Antiseptic Wet Wipes 97Aspartame Granules in Sachets 98Aspartame Powder in Sachets 98Aspartame Tablets 99Aspartame Tablets 99Aspartame Tablets 100Aspartame Tablets, Effervescent 100Aspirin, Acetaminophen, and Caffeine Tablets 100Aspirin, Acetaminophen, Caffeine, and Salicylamide Tablets 101Attapulgite Tablets 102Baby Cream, Benzalkonium Chloride and Zinc Oxide 103Baby Lotion 104Baby Shampoo 104Basic Cream for Varioius Active Ingredients 105Benzalkonium Chloride Contraceptive Gel 105Benzyl Benzoate Solution 105Benzoyl Peroxide and a-Bisabolol Gel 106Benzoyl Peroxide Anti-Acne Cream 106Benzoyl Peroxide Anti-Acne Gel 107Benzoyl Peroxide Anti-Acne Lotion 107Benzoyl Peroxide Anti-Acne Microemulsion 108Berberine Tablets 108Beta-Carotene Effervescent Tablets 108Beta-Carotene Tablets 109Beta-Carotene Tablets 109Beta-Carotene Tablets 109Beta-Carotene, Vitamin C, and Vitamin E Chewable Tablets.Beta-Carotene, Vitamin C, and Vitamin E TabletsBeta-Carotene, Vitamin C, and Vitamin E TabletsBeta-Carotene, Vitamin C, and Vitamin E TabletsBeta-Carotene, Vitamin C, and Vitamin E TabletsBetamethasone and Neomycin Gel-CreamBetamethasone CreamBetamethasone GelBetamethasone Valerate CreamBetamethasone Valerate OintmentBisacodyl Delayed-Release TabletsBisacodyl SuppositoriesBismuth Carbonate SuspensionBismuth Subsalicylate SuspensionBran TabletsBreast Care CreamBromhexine Hydrochloride SyrupBromhexine Hydrochloride Syrup. Alcohol Free.Bromhexine Hydrochloride TabletsBurn CreamBurn CreamCaffeine TabletsCalamine CreamCalamine CreamCalamine LotionCalcium and Vitamin D TabletsCalcium Carbonate and Glycine Tablets

1010I1

31414151516161617IS191920202121

Calcium Carbonate and Vitamin D Tablets 123Calcium Carbonate Tablets 124Calcium D-Pantothenate Chewable Tablets 124Calcium D-Pantothenate Tablets 124Calcium D-Pantothenate Tablets 125Calcium Effervescent Tablets 125Calcium Gluconate Tablets 126Calcium Glycerophosphate Tablets 126Calcium Glycerophosphate Tablets 126Calcium Iodide and Ascorbic Acid Syrup 127Calcium Phosphate Tablets for Cats and Dogs (Direct Compression) 127Calcium Phosphate Tablets for Cats and Dogs 128Carbinoxamine Maleate, Phenylpropanolamine, and Acetaminophen Sustained-Re lease Tablets 128Carbonyl Iron, Copper Sulfate, and Manganese Sulfate Tablets 129Carnitine and Coenzyme Q Solution 129Cetrimide Antiseptic Cream 129Charcoal Tablets 130Chlophedianol, Ipecac, Ephedrine, Ammonium Chloride, Carbinoxamine, and Balsam Tolu Syrup 131Chlorhexidine Gel 131Chlorhexidine Lozenges 132Chlorpheniramine Maleate Syrup 132Chymotrypsine Tablets 133Citrate Effervescent Powder 133Crospovidone Effervescent Tablets 134Crospovidone Water Dispersible Tablets 134Cyanocobalamin Tablets 135Dexpanthenol Gel-Cream 135Dextromethorphan, Pseudoephedrine, and Chlorpheniramine Maleate Syrup 136Dihydroxyaluminum Sodium Carbonate Tablets 136Dimenhydrinate Tablets 137Dimenhydrinate Tablets 137Dimenhydrinate Tablets 137Diphenhydramine Hydrochloride Tablets 138Econazole Nitrate and Benzoyl Peroxide Anti-Acne Cream 138Econazole Nitrate and Benzoyl Peroxide Anti-Acne Lotion 139Eucalyptol Solution 139Eucalyptus and Mint Emulsion 139Eucalyptus and Mint Ointment 140Ferrous Fumarate Tablets 140Ferrous Sulfate, Manganese Sulfate, and Copper Sulfate Tablets 140Ferrous Sulfate Oral Solution 141Ferrous Sulfate Oral Syrup 141Ferrous Sulfate Tablets 142Fir Needle Oil Solution 142Folic Acid Tablets 143Folic Acid Tablets 143Foot Bath 144Foot Freshener Cream 144Foot Mousse 145Garlic Tablets 145Glycerin Suppositories 146Glycerin Suppositories for Children 146Glycol Foam, Nonaqueous 146Guaifenesin Pseudoephedrine. Carbinoxamine, and Chlophedianol Drops 147Hemorrhoid Cream 148

Horsetail Extract Tablets 148Hydrocortisone Aqueous Gel 149Hydrocortisone Aqueous Gel 149Hydrocortisone Cream 150Hydrocortisone Cream 150Hydrocortisone Ethanolic Gel 151Hydrocortisone Ointment 151Ibuprofen Pediatric Suspension 152Ibuprofen Tablets 153Inosin Tablets 154Insect Bite Cream 155Iron (Polymer Coated Particle) Tablets 155Iron Infant Drops 156Iron Polystyrene and Vitamin C Syrup 157Kaolin-Pectin Suspension 158Kaolin-Pectin Tablets 159Keratolytic Cream 160Khellin Tablets 160Lidocaine Gel 161Lidocaine Gel-Cream 161Lidocaine Ointment 162Lidocaine, Eugenol, and Menthol Dental Ointment 162Loratidine Tablets 163Loratidine Fastab 163Magaldrate Chewable Tablets 164Magaldrate Dispersible Tablets 164Magaldrate Instant Powder or Dry Syrup 165Magaldrate Suspension 165Magaldrate Tablets 166Magaldrate with Simethicone Suspension 167Magaldrate with Simethicone Tablet 168Magnesium Carbonate Tablets 169Medicated Foot Cream 169Methyl Salicylate Heat Rub Lotion 170Methyl Salicylate Analgesic Cream 170Methyl Salicylate Analgesic Cream 171Methyl Salicylate and Menthol Gel 171Metoclopramide Tablets 172Miconazole Nitrate Cream 172Mineral and Multivitamin Syrup 173Mint-Menthol Mouthwash 174Menthol Mouthwash 175Mint Oil Solution 175Multivitaminm, Calcium, and Iron Tablets 176Multivitamin and Calcium Syrup 176Multivitamin and Carbonyl Iron Tablets 177Multivitamin and Mineral Tablets with Beta Carotene 177Multivitamin and Mineral Syrup I 7SMultivitamin and Mineral Tablets ISOMultivitamin Chewable Tablets for Children isiMultivitamin Drops ISIMultivitamin Effervescent Granules 1S2Multivitamin Effervescent Tablets with Beta Carotene 1 S3Multivitamin Effervescent Tablets IS4Multivitamin Effervescent Tablets IS5

Multivitamin Infant Drops 186Multivitamin Infant Drops 187Multivitamin Instant Granules 188Multivitamin Mineral Syrup 189Multivitamin Oral Gel with Linoleic and Linolenic Acid 190Multivitamin Oral Gel Veterinary 191Multivitamin Syrup 192Multivitamin Syrup 192Multivitamin with Beta-Carotene Tablets 193Multivitamin Tablets with Beta-Carotene 193Multivitamin and Beta-Carotene Tablets 194Multivitamin Tablets 195Multivitamin Tablets 196Multivitamin Tablets 197Multivitamin Tablets 198Multivitamin Tablets 198Multivitamin Tablets for Dogs 199Multivitamin and Fluoride Chewable Tablets 200Multivitamin with Fluoride Infant Drops 201Multivitamin with Zinc Tablets 202Naphazoline Eye Drops 203Neomycin Gel 203Nicotinamide Tablets 204Nicotinic Acid (Niacin) Tablets 204Nondetergent Neutral Dry Skin Cream 204Norephedrine Syrup 205Nystatin Cream 206Nystatin Ointment 207Nystatin, Neomycin Sulfate, Gramicidin, and Triamcinolone Acetonide Cream 208Nystatin, Neomycin Sulfate, Gramicidin, and Triamcinolone Acetonide Ointment 209Omega Fatty Acids Tablets 209Oral Rehydration Salt (45 mEq) 210Pancreatin Tablets 210Pancreatin Tablets 211Pancreatin and Cholic Acid Tablets 211Panthenol Lotion 212Panthenol Ointment 213Peppermint Rub Cream 213Phenindion Tablets 214Phenolphthalein Tablets 214Phenolphthalein Tablets 214Phenylpropanolamine Hydrochloride Tablets 215Phenylpropanolamine, Chlorpheniramine, Dextromethorphan, Vitamin C Syrup 216Placebo Tablets 217Polidocanol Wound Spray 217Polyvinylpyrrolidone-Iodine Mouthwash 217Povidone-Iodine and Lidocaine Gel 218Povidone-Iodine Bar Soap 218Povidone-Iodine Bar Soap 218Povidone-Iodine Bar Soap 219Povidone-Iodine Concentrates for Broilers and Cattle 219Povidone-Iodine Cream 219Povidone-Iodine Effervescent Vaginal Tablets 220Povidone-Iodine Foam Spray 220Povidone-Iodine Gargle 220

Povidone-Iodine Gargle Solution Concentrate 221Povidone-Iodine Gel-Cream 221Povidone-Iodine Gels 221Povidone-Iodine Glucose Ointment 222Povidone-Iodine Liquid Spray 222Povidone-Iodine Lozenges 222Povidone-Iodine Mastitis Cream for Cattle 223Povidone-Iodine Mouthwash and Gargle Solution Concentrate 223Povidone-Iodine Powder Spray 223Povidone-Iodine Pump Spray 224Povidone-Iodine Shampoo 224Povidone-Iodine Soft Gel 224Povidone-Iodine Solution 225Povidone-Iodine Solution 225Povidone-Iodine Solution 226Povidone-Iodine Solution 226Povidone-Iodine Solution 226Povidone-Iodine Scrub 227Povidone-Iodine Surgical Scrub 227Povidone-Iodine Surgical Scrub 228Povidone-Iodine Transparent Ointment 228Povidone—Iodine Vaginal Douche Concentrate 228Povidone-Iodine Vaginal Ovule 229Povidone-Iodine Vaginal Ovule 229Povidone-Iodine Viscous Solution 229Promethazine Hydrochloride Syrup 230Promethazine Hydrochloride Tablets 231Pseudoephedrine Hydrochloride Capsules 232Pseudoephedrine Hydrochloride Syrup 232Pseudoephedrine Hydrochloride Tablets 233Pseudoephedrine Tablets 233Pseudoephedrine Hydrochloride, Carbinoxamine Maleate Oral Drops 234Psoriasis Cream 234Psoriasis Cream 235Pyridoxine Tablets 235Pyridoxine Tablets 235Pyridoxine Tablets 236Pyridoxine Tablets 236Pyridoxine Tablets 236Pyridoxine Tablets 237Ranitidine Tablets 237Ranitidine Hydrochloride Tablets 238Riboflavin Tablets 23SRiboflavin Tablets 238Riboflavin Tablets 239Riboflavin Tablets 239Riboflavin Tablets 239Rubefacient Analgesic Ointment 240Saccharin Effervescent Tablets 240Saccharin Tablets 241Saccharin Tablets 241Salicylic Acid Cream 242Selegiline Tablets 242Selenium Sulfide Shampoo with Conditioner 243Serratio Peptidase Tablets 243

Silicone Protective Cream 244Silimarin Tablets 244Simethicone Chewable Tablets 244Simethicone Chewable Tablets 245Simethicone Tablets 245Sodium Fluoride Tablets 246Sodium Fluoride Tablets 246Spirulina Extract Chewable Tablets 246Sucralfate and Sodium Alginate Tablets 247Sulfur Antiseptic Ointment 247Tannin-Crospovidone Complex Tablets 248Tetrahydrozoline Eye Drops 248Thiamine and Caffeine Tablets 249Thiamine Hydrochloride Tablets 249Thiamine Hydrochloride Tablets, Sugar-Coated 250Thiamine, Pyridoxine, and Cyanocobalamine Tablets 251Thiamine, Pyridoxine, and Cyanocobalamine Tablets 252Thiamine, Pyridoxine, and Cyanocobalamine Tablets 252Thiamine, Pyridoxine, and Cyanocobalamine Tablets 253Thiamine, Pyridoxine, and Cyanocobalamine Tablets 253Thiamine Tablets 253Thiamine Tablets 254Thiamine Tablets 254Thiamine Tablets 254Thiamine Tablets 255Tolnaftate and Undecylanate Foot Care Cream 255Tolnaftate Foot Care Microemulsion 256Tolu Balsam Cough Syrup 257Triclosan and Zinc Foot Deodorant Powder 258Triclosan Foot Care Cream 258Triprolidine and Pseudoephedrine Hydrochloride Syrup 259Triprolidine and Pseudoephedrine Hydrochloride Tablets 260Trolamine Salicylate Cream 260Ultrasonic Adhesive Gel 261Urea Peroxide Ear Drops 261Valeriana and Passiflora Extract Tablets 262Vitamin A and Vitamin D Infant Drops 263Vitamin A and Vitamin D3 Drops 264Vitamin A and Vitamin D3 Oral Solution 264Vitamin A and Vitamin D3 Syrup 264Vitamin A and Vitamin E Drops 265Vitamin A and Vitamin E Drops (25,000 IU/50 mg/mL) 265Vitamin A and Vitamin E Tablets 265Vitamin A Chewable Tablets 266Vitamin A Concentrate, Water-Miscible 266Vitamin A Drops 266Vitamin A Suppositories 267Vitamin A Tablets 267Vitamin A Tablets 267Vitamin A Tablets 268Vitamin A Tablets 268Vitamin A Tablets 268Vitamin A. Vitamin B6, and Vitamin E Tablets 269Vitamin A. Vitamin C, and Vitamin D3 Chewable Tablets 269Vitamin A. Vitamin C. and Vitamin E Tablets (1200 IU/60 mg/30 mg) 270

Vitamin B-Complex, Amino Acids, and Magnesium Effervescent Granules (Sugar-Free) 270Vitamin B-Complex and Carnitine Tablets 271Vitamin B-Complex and Folic Acid Dragees 272Vitamin B-Complex and Iron Syrup 273Vitamin B-Complex and Vitamin C Effervescent Tablets 274Vitamin B-Complex and Vitamin C Instant Granules 275Vitamin B-Complex and Vitamin C Syrup 275Vitamin B-Complex and Vitamin C Syrup 276Vitamin B-Complex and Vitamin C Tablets 276Vitamin B-Complex and Vitamin C Tablets 277Vitamin B-Complex, Choline, and Bile Tablets 277Vitamin B-Complex Syrup 278Vitamin B-Complex Syrup 279Vitamin B-Complex Syrup (without B12) 280Vitamin B-Complex Tablets 281Vitamin B-Complex Tablets 281Vitamin B-Complex Tablets 282Vitamin B-Complex, Vitamin A, Vitamin C, and Vitamin D Syrup 283Vitamin B-Complex, Vitamin A, Vitamin C. and Vitamin D Tablets 284Vitamin B-Complex, Vitamin A, Vitamin C. Vitamin D. and Calcium Drops 285Vitamin B-Complex, Vitamin A, Vitamin C. Vitamin D. and Mineral Tablets 286Vitamin B-Complex, Vitamin A, Vitamin C. Vitamin D. and Vitamin F Pediatric Drops 287Vitamin B-Complex, Vitamin C, and Calcium Effervescent Tablets 28SVitamin B-Complex, Vitamin C, and Ferrous Sulfate Tablets 288Vitamin B-Complex, Vitamin C, and Iron Syrup 289Vitamin B-Complex, Vitamin C. and Iron Syrup 290Vitamin B-Complex, Vitamin C, and Vitamin E Tablets 291Vitamin C and Calcium Carbonate Effervescent Tablets (500 mg/300 mg) 292Vitamin C and Vitamin E Lozenges 292Vitamin C Chewable Tablets 293Vitamin C Chewable Tablets 293Vitamin C Chewable Tablets 294Vitamin C Chewable Tablets 294Vitamin C Chewable Tablets 295Vitamin C Chewable Tablets with Dextrose 295Vitamin C Chewable Tablets with Fructose 296Vitamin C Chewable Tablets with Sucrose 296Vitamin C Drops 296Vitamin C Effervescent Tablets 2l)7Vitamin C Effervescent Tablets 29NVitamin C Effervescent Tablets 29SVitamin C Effervescent Tablets 299Vitamin C Tablets 299Vitamin C Tablets 300Vitamin C Tablets ^00Vitamin E and Bcnzocaine Solution 300Vitamin E Chewable Tablets ^01Vitamin E Chewable Tablets M)\Vitamin E Chewable Tablets 3d IVitamin E Concentrate. Water-Miscible 3d2Vitamin E Drops >d2Vitamin E Gel-Cream 3d2Vitamin E Softgel Capsules ^03Vitamin E Solution with Ethanol 3d3Vitamin E Tablets M)>

Vitamin E Tablets 304Zinc Oxide Lotion 304Zinc Oxide Ointment 305Zinc Pyrithione Shampoo 305Zinc Undecylenate Cream 306Zirconium Oxide Lotion 306

Part IIIAppendix 307I. Introduction 309II. Hydroxypropyl Methylcellulose (Methocel, HPMC) Aqueous Coatings 310

A. BriteRose 310B. Cherry Red 310C. Geranium Rose 310D. Gloss 311E. Red 311E Moderate Red 311G. Clear 312H. Green 312I. Holberry Red 312J. Sun Orange 313K. Opadry Yellow 313L. Opadry Yellow 313M. Opadry Red 314N. Opadry Green 314O. White Coating 315

III. Hydroxypropyl Methylcellulose Opaque Organic Coating 315A. Brite Green 315B. Red Mahogany 316C. Sun Orange 316D. Dark Red 316E. Deep Yellow 316E Pale Yellow 317G. Scarlet Red 317

IV. Hydroxypropyl Methyl Cellulose/Hydroxypropyl Cellulose (Klucel®) Coating 317A. White 317

V. Hydroxypropyl Methyl Cellulose/Ethyl Cellulose Coating 318A. Reddish Orange Opaque 318B. Subcoating Solution 318

VI. Hydroxy Methyl Cellulose/Hydroxy Cellulose Coating 319A. Blue 319B. Clear (50:50) 319

VII. Hydroxy Methyl Cellulose/Ethyl Cellulose Coating 320A. Clear 320

VIII. Polyvinylpyrrolidone (PVP) Coatings 320A. Subcoating 320B. Kollidon® VA 64 (Polyvinylpyrrolidone/Vinylacetate Copolymer, BASF) 321C. Kollidon® VA 64 and Polyvinyl Alcohol 322D. Kollidon® 30 and Shellac 322E. Kollidon® VA 64 and Hydroxypropyl Methyl Cellulose 323F. Povidone, Ethyl Cellulose, and Talc 323

IX. Cellulose Acetate Phthalate and Carbowax Coatings 324A. Brite Green 324B. Cherry Red 324C. Clear 324D. Orange 324E. Red Mahogany 324E Orange 324

X. Sugar Coatings 325A. Basic 325B. Automatic 326C. Manual, White 326

XI. Enteric Coatings 327A. Kollicoat® and Kollidon® Enteric Film Coating 327

XII. Eudragit® Enteric Aqueous 328A. Brick Red 328B. Yellow 328C. Brown 328D. Dark Orange 329E. Orange 329F. Dispersed Orange 329

XIII. Hydroxypropyl Methyl Cellulose Phthalate Enteric Coating 330A. Clear Enteric 330B. Orchid Pink Opaque 330C. Light Apricot Orange 330

Index 331