388367563.pdf

H A N D B O O K O F

PharmaceuticalManufacturingFormulationsCompressed Solid Products

VOLUME 1

Sarfaraz K. Niazi

CRC PRESSBoca Raton London New York Washington, D.C.

Table of Contents

PartiRegulatory and Manufacturing Requirements in CompressedSolid Dosage Forms

Chapter 1Bioavailability and Bioequivalence Studies for Orally Administered Drug Products 3I. Introduction 3II. Background 3

A. General 3B. Bioavailability 4C. Bioequivalence 4

1. INDs/NDAs 42. ANDAs 53. Postapproval Changes 5

III. Methods to Document BA and BE 5A. Pharmacokinetic Studies 5

1. General Considerations 52. Pilot Study 63. Pivotal Bioequivalence Studies 64. Study Designs 65. Study Population 66. Single-Dose/Multiple-Dose Studies 67. Bioanalytical Methodology 68. Pharmacokinetic Measures of Systemic Exposure 7

B. Pharmacodynamic Studies 7C. Comparative Clinical Studies 7D. In Vitro Studies 7

IV. Comparison of BA Measures in BE Studies 8V. Documentation of BA and BE 8

A. Solutions 9B. Suspensions 9C. Immediate-Release Products: Capsules and Tablets 9

1. General Recommendations 92. Waivers of In Vivo BE Studies (Biowaivers) 9

D. Modified-Release Products 101. NDAs: BA and BE Studies 102. ANDAs: BE Studies 103. Waivers of In Vivo BE Studies (Biowaivers): NDAs and ANDAs 14. Postapproval Changes 1

E. Miscellaneous Dosage Forms 1VI. Special Topics 1

A. Food-Effect Studies 1B. Moieties to Be Measured 1

1. Parent Drug vs. Metabolites 12. Enantiomers vs. Racemates 123. Drug Products with Complex Mixtures as the Active Ingredients 12

C. Long Half-Life Drugs 12D. First Point Cmax 13E. Orally Administered Drugs Intended for Local Action 13F. Narrow Therapeutic Range Drugs 13

Appendix 1A — General Pharmacokinetic Study Design and Data Handling 15

Chapter 2Guidance on Formulating Compressed Solids 17I. Abbreviated Directions 17II. API 17III. Bio vs. Production Batches 17IV. Cleaning Validation 17V Coatings 17VI. Compliance with Regulatory Requirements 18VII. Compression Process Control 18VIII. Content Uniformity 18IX. Cross-Contamination 18X. Desegregation of Powders 18XI. Disintegration Test 19

A. Uncoated Tablets 19B. Plain Coated Tablets 19C. Delayed-Release (Enteric-Coated) Tablets 19D. Buccal Tablets 19E. Sublingual Tablets 19

XII. Dissolution 19XIII. Disintegration and Dissolution 20XIV. Drug Substance Characterization 20XV Drying Process 20XVI. Dyes in Formulations 20XVII. Equipment 20

A. Blenders 201. Pony Pan 212. Ribbon 213. Tumbler 214. High-Shear (High-Energy) 215. Plastic Bag 22

B. Dryers 22C. Tablet Compression Equipment 22D. Coating Equipment 22

XVIII. Excipients 23A. Coating Agent 23B. Glidant 23C. Tablet Binder 23D. Diluent 23E. Disintegrant 23F. Lubricant 23

XIX. Fill Weights 24XX. Final Packaging 24XXI. Final Testing 25XXII. Fines 25XXIII. Formula Excesses 25XXIV. Geometric Dilution 25XXV. Granulation/Mix Analysis 25XXVI. Ingredient Warning 26

XXVII. In-Process Testing 26XXVIII. Loss on Drying (LOD) 26XXIX. Manufacturing Yields 27XXX. Master Formula 27XXXI. Multiple-Item Entries 27XXXII. Multiple Strengths of Formulations 27XXXIII. Novel Drug Delivery Systems 27XXXIV. Particle Coating 28XXXV. Preservatives in Compressed Solid Dosage Formulations 28XXXVI. Punch Size and Shape 28XXXVII. Reworking Culls 28XXXVIII. Scale-Up 28XXXIV Segregation 29XXXV. Sifting Ingredients and Granules 29XXXVI. Specifications 29XXXVII. Stability Testing 29XXXVIII. Storage of In-Process Material 30XXXIX. Tablet Friability 30XL. Tablet Manufacturing 30XLI. Tablets 30XLII. Water-Purified USP 31XLIII. Weight Variation and Content Uniformity 31XLIV. Wet Granulation vs. Dry Granulation or Direct Compression 32

Part IICompressed Solid Formulations 33Acetaminophen, Ibuprofen, and Orphenadrine Tablets (250 mg/200 mg/200 mg) 35Acetaminophen, Norephedrine, and Phenyltoloxamine Tablets (300 mg/25 mg/22 mg) 35Acetaminophen and Phenprobamat Tablets (200 mg/200 mg) 36Acetaminophen and Orphenadrine Citrate Tablets (450 mg/35 mg) 37Acetaminophen Tablets, Chewable 38Acetaminophen, Dextropropoxyphen Hydrochloride Tablets (325 mg/32 mg) 39Acetaminophen and Codeine Tablets [34] 40Acetaminophen, Salicylamide, Caffeine, and Codeine Tablets (150 mg/200 mg/50 mg/10 mg) 41Acyclovir Tablets [162] 42Acyclovir Water-Dispersible Tablets (800 mg) 42Albendazole Tablets (200 mg) 43Alendronate Tablets [38] 44Alendronate Tablets, Effervescent (10 mg) 44Alendronate Sodium Tablets (50 mg) 44Allopurinol Tablets (100 mg) [84] 45Allopurinol Tablets (300 mg) 46Alprazolam Tablets (0.25 mg/0.50 mg/1.0 mg) 474-Amino-l-hydroxybutylidene-l.l-bisphosphonic Acid Tablets (5 mg) 48Aminophylline Tablets (100 mg) 48Amiodarone Tablets (200 mg) 49Amlodipine Besylate Tablets |9] 50Amitriptyline Tablets (50 mg) [42] 51Amoxicillin Tablets (250 mg/500 mg/1 g) 52Amoxicillin Trihydrate and Clavulanate Potassium Tablets (500 mg/125 mg) 53Amoxicillin and Potassium Clavulanate Tablets (250 mg/62.5 mg) 54Amphetamine Salts Tablets 54Atenolol Tablets (50 mg/100 mg) 55

Atorvastatin Tablets (10 mg/20 mg) 57Azithromycin Tablets (250 mg) 58Benzafibrate Tablets (200 mg) 59Benazepril Hydrochloride Tablets 60Betamethasone Tablets (0.50 mg) 61BIRB 796 Tablets (100 mg) 61Bisoprolol Fumarate and Hydrochlorothiazide Tablets 62Bromazepam Tablets (3 mg) 62Bromhexine Tablets (8 mg) 63Bromocriptine Tablets 63Bufiomedil Hydrochloride Tablets (150 mg/300 mg) 64Buflomedil Hydrochloride Tablets (600 mg) 65Bupropion Hydrochloride Tablets 66Buspirone Hydrochloride Tablets 67Buspirone Hydrochloride Tablets, Controlled-Release (30 mg) 67Captopril Tablets (25 mg) 68Carbamazepine Tablets (200 mg) 69Carbamazepine Tablets (200 mg) 70Carbidopa and Levodopa Tablets 70Carisoprodol Tablets 71Carvedilol Tablets 71Cefadroxil Dispersible Tablets (250 mg) 72Cefdinir Tablets (300 mg) 72Cefixime Tablets (400 mg) 73Cefprozil Tablets (250 mg) 73Celecoxib Tablets 74Cephalexin Tablets 74Cetirizine and Pseudoephedrine Delayed-Release Tablets (5 mg/120 mg) 74Cetirizine Hydrochloride Tablets (10 mg) 75Chlorcyclizine Hydrochloride Tablets (50 mg) 75Chlordiazepoxide and Clinidium Bromide Tablets (5 mg/2.5 mg) 76Chlordiazepoxide Tablets (10 mg) 76Chloroquine Tablets (250 mg) 77Choline Theophyllinate Tablets (100 mg) 77Chymotrypsine Tablets (25 mg) 77Cilazapril Tablets (2.5 mg) 78Cimetidine Tablets (200 mg) 79Ciprofloxacin Tablets (500 mg) 80Ciprofloxacin Tablets (750 mg) 81Cisapride Tablets (5 mg) 82Citalopram Hydrobromide Tablets 82Clarithromycin Tablets (250 mg/500 mg) 83Clenbuterol Tablets (20 meg) 84Clindamycin Tablets (20 mg) 84Clobazam Tablets (10 mg) 85Clomifen Citrate Tablets (50 mg) 85Clomipramine Hydrochloride Tablets, Effervescent (300 mg) 85Clomipramine Hydrochloride Tablets, Buccal (10 mg) 86Clonazepam Tablets (1 mg/2 mg) 86Clonidine Tablets (0.1 mg/0.2 mg/0.3 mg) 86Clopidogrel Bisulfate Tablets (75 mg) 87Codeine, Acetaminophen, and Pentobarbital Tablets (15 mg/300 mg/30 mg) 87Conjugated Estrogens (0.3-2.50 mg) 88Conjugated Estrogens and Medroxyprogesterone Tablets 89Coumadin Tablets 89

Cyclobenzaprine Hydrochloride Tablets (10 mg) [64] 90Cyproheptadine Tablets (4 mg) 90Dapsone Tablets (50 mg) 91Desloratidine Tablets (5 mg) 91Desogestrel and Ethinyl Estradiol Tablets (0.15 mg/0.03 mg) 91Diazepam Tablets (2 mg/5 mg/10 mg) 92Diclofenac Sodium Tablets (25 mg) 93Diclofenac Sodium Tablets (50 mg) 94Diclofenac Sodium Tablets (100 mg) 94Didanosine Tablets (50 mg) 95Diethylcarbamazine Tablets (100 mg) 95Difenoxin and Atropine Tablets (0.5 mg/0.025 mg) 96Digoxin Tablets (0.125 mg/0.25 mg) [92] 96Diltiazem Hydrochloride Tablets (60 mg) 97Diltiazem Tablets 60 mg [95] 98Diphenoxylate Hydrochloride and Atropine Sulfate Tablets (2.5 mg/0.025 mg) 98Divalproate Sodium Tablets (125 mg) [121] 99Divalproex Sodium Tablets (400 mg) 100Doxazosin Mesylate Tablets (1 mg/2 mg/4 mg/8 mg) [112] 100Doxycycline Hydrochloride Tablets (100 mg) [91] 101Enalapril Maleate Tablets (2.5 mg/5 mg/10 mg/20 mg) [66] 102Enalapril Maleate Tablets (10 mg) 102Enoxacin Tablets (400 mg) 103Erythromycin Ethylsuccinate Tablets (400 mg) 104Erythromycin Particle-Coated Tablets (150 mg) 105Erythromycin Tablets (100 mg) 106Erythromycin Tablets (100 mg) 106Erythromycin Tablets (500 mg) 107Estazolam Tablets (1 mg) 109Estazolam Tablets (2 mg) 109Estradiol Tablets (0.5 mg/1 mg/2 mg) [85] 110Estropipate Tablets (0.626 mg/1.25 mg/2.25 mg/5 mg) 110Ethambutol Tablets (400 mg) 111Ethambutol Tablets (800 mg) 112Etophylline and Theophylline Tablets (100 mg/22 mg) 113Etophylline and Theophylline Tablets (100 mg/22 mg) 113Famciclovir Tablets (125 mg/250 mg) 114Famotidine Tablets (20 mg) [146] 115Famotidine Tablets (40 mg) 116Fexofenadine Tablets (30 mg/60 mg/180 mg) [26] 116Fexofenadine and Pseudoephedrine Tablets (10 mg/240 mg) [111] 117Finasteride Tablets (5 mg) 118Fluconazole Tablets (50 mg/100 mg/200 mg) [75] 118Fluvoxamine Maleate Tablets (50 mg) 119Fluoxetine Hydrochloride Tablets (10 mg/20 mg/40 mg) [33] 120Fluoxetine Hydrochloride Tablets (12.5 mg/25.0 mg) Controlled-Release Bilayer 121Fosinopril Tablets (20 mg) [ 133] 122Fucidine Tablets (125 mg) 122Furazolidone Tablets (100 mg) 123Furosemide Tablets (40 mg) [7] 123Furosemide Tablets (40 mg) 124Furosemide Tablets (200 mg) 125Gabapentin Tablets (600 mg) 125Galanthamine Hydrobromide Tablets (1 mg) 126Gemfibrozil Tablets (600 mg) [114] 127

Glibenclamide Tablets (2.5 mg) 128Glibenclamide Tablets (5 mg) 129Gliclazide Tablets (80 mg) 130Glimepiride Tablets (1 mg/2 mg) [129] 131Glipizide Tablets (5 mg) [71] 132Glipizide Tablets CR (5 mg) 133Glyburide and Metformin Tablets (250 mg/500 mg; 1.25 mg/2.50 mg) [124] 134Glyburide Tablets (5 mg) [81] 135Griseofulvin Tablets (125 mg) 136Griseofulvin Tablets (500 mg) 136Hydrochlorothiazide and Potassium Chloride (50 mg/300 mg) 137Hydrochlorothiazide Tablets (50 mg) [10] 137Hydrochlorothiazide Tablets (50 mg) 138Hydrocodone and Acetaminophen Tablets (5.0 mg/500 mg; 7.50 mg/750 mg) 139Hydrocodone and Ibuprofen Tablets 140Hydroxyzine Tablets [132] 140Hyoscine Butyl Bromide Tablets (10 mg) 141Ibuprofen Tablets (400 mg) [19] 142Ibuprofen Tablets (400 mg) 143Ibuprofen Tablets (600 mg) 144Imipramine Tablets (25 mg) 144Irbesartan Tablets (75 mg/150 mg/300 mg) [149] 145Isoniazid Tablets (100 mg) 146Isosorbide Dinitrate Tablets (5 mg) [68] 147Isosorbide Dinitrate Tablets (10 mg) 147Ketotifen Tablets (1 mg) 148Lamotrigine Tablets (100 mg) 148Lansoprazole Tablets (10 mg or 20 mg) 149Lansoprazole Tablets (10 mg or 20 mg) 149Lansoprazole Tablets Chewable (10 mg/20 mg) 149Lansoprazole Tablets, Rapid Dissolution (20 mg) 150Levamisole Hydrochloride Tablets (40 mg) 150Levamisole Tablets (150 mg) 151Levofloxacin Tablets (250 mg) [69] 151Levothyroxine Tablets [4] 151Levothyroxine Tablets (50 meg) [25] 152Levothyroxine Tablets (0.025 mg) 152Linezolid Tablets (400 mg) 153Lisinopril Tablets (10 mg) [52] 153Lomefloxacin Hydrochloride Tablets (400 mg) 154Loperamide Hydrochloride Tablets (2 mg) 154Loratadine and Pseudoephedrine Sulfate Tablets (10 mg/240 mg) [127] 155Loratadine Tablets (10 mg) [32] 156Lorazepam Tablets (0.50 mg/1 mg/2 mg) [37] 157Losartan and Hydrochlorothiazide Tablets (50 mg/12.5 mg) [118] 157Losartan Potassium Tablets (50 mg) [93] 158Mebendazol Tablets (100 mg) 159Meclizine Hydrochloride Tablets (25 mg) [135] 159Medroxyprogesterone Acetate Tablets (2.5 mg/5 mg/10 mg) [89] 159Mefanamic Acid and Dicyclomine Hydrochloride Tablets (250 mg/10 mg) 160Mefenamic Acid Tablets (250 mg) 160Mefloquine Hydrochloride Tablets (250 mg) 161Meprobamate and Phenobarbital Tablets (400 mg/30 mg) 161Meprobamate and Phenobarbital Tablets (400 mg/30 mg) 162Meprobamate Tablets (400 mg) 162

Meprobamate Tablets (400 mg) 163Metamizol Tablets (500 mg) 163Metamizol Tablets (500 mg) 164Metformin Hydrochloride Tablets, Extended Release (500 mg) 165Metformin Tablets (500 mg) [40] 166Metformin Tablets, Extended Release (500 mg) 167Methenamine Tablets (500 mg) 167Methyclothiazide and Deserpidine Tablets (5 mg/0.25 mg) 168Methyclothiazide Tablets (5 mg) 169Methylergotamine Malate Tablets (0.5 mg) 170Methylphenidate Hydrochloride Tablets Extended Release (18 mg/36 mg) [122] 170Methylprednisolone Tablets (2 mg/4 mg/8 mg/16 mg/24 mg/32 mg) [99] 171Metoclopramide Tablets (10 mg) [138] 171Metoclopramide Tablets (20 mg) 172Metoprolol Succinate Tablets (95 mg) [21] 173Metoprolol Tartrate Tablets [36] 173Metronidazole Effervescent Vaginal Tablets (500 mg) 174Metronidazole, Furazolidone, and Loperamide Tablets (200 mg/25 mg/2 mg) 174Metronidazole Tablets (200 mg) 175Metronidazole Tablets (200 mg/400 mg) 176Metronidazole Tablets (400 mg) [147] 177Metronidazole Tablets (500 mg) 177Mirtazapine Tablets [145] 178Montelukast Sodium Tablets (5 mg) [54] 178Nalidixic Acid Tablets (500 mg) 179Nalidixic Acid Tablets (500 mg) 179Naproxen Tablets (250 mg) [58] 180Naproxen Tablets (250 mg/500 mg) 181Naproxen Tablets (450 mg) 182Neomycin Tablets (250 mg) 182Nifedipine Tablets (5 mg) 183Nifedipine Tablets (10 mg) 183Nimesulide Dispersible Tablets (100 mg) 184Nitrendipine Tablets (25 mg) 184Nitrofurantoin Tablets (100 mg) 185Nitrofurantoin Tablets (100 mg) 185Nitroglycerine Tablets (0.3 mg) 186Noramidopyrine Methansulfonate and Dicyclomine Hydrochloride Tablets (500 mg/10 mg) 187Norethindrone and Ethinyl Estradiol Tablets (0.75 mg/0.035 mg; 0.50 mg/0.035 mg: 1.0 mg/O.O35 mg) [1311 188Norfloxacin Tablets (400 mg) 189Norgestimate and Ethinyl Estradiol Tablets (0.18 mg/0.035 mg: 0.215 mg/0.035; 0.25 mg/0.035 mg) [27] 190Nystatin Tablets (50 mg) 190Nystatin Tablets (200 mg) 191Olanzapine Tablets [110] 191Omeprazole and Ibuprofen Tablets (10 mg/400 mg) 192Omeprazole Tablets (10 mg/20 mg) 192Omeprazole Tablets (10 mg/20 mg) 193Omeprazole Tablets, Chewable (10 mg/20 mg) 193Omeprazole Tablets, Rapid Dissolution (20 mg) 193Oxybutynin Chloride Tablets (5 mg/10 mg) [194] 194Oxycodone Hydrochloride and Acetaminophen Tablets (5 mg/325 mg) (90] 195Oxycodone Hydrochloride Tablets (5 mg) [119] 196Oxytetracycline Tablets (250 mg) 196Pantoprazole Tablets [77] 1%Pantoprozole Tablets (10 mg/20 mg) 197

Pantoprazole Tablets, Chewable (10 mg/20 mg) 197Pantoprazole Tablets, Rapid Dissolution (20 mg) 198Para Amino Salicylic Acid Tablets (500 mg) 199Paroxetine Hydrochloride Tablets (10 mg/20 mg/30 mg/40 mg) [15] 200Penicillin Chewable Tablets (125 mg) [103] 201Perfloxacin Tablets (400 mg) 202Phendimetrazin Tablets (35 mg) 202Phenindion Tablets (50 mg) 203Phenoxymethyl Penicillin Potassium Tablets (250 mg) 204Phenylbutazone Tablets (100 mg) 205Phenylpropanolamine Hydrochloride Tablets (60 mg) 206Phenytoin Sodium Tablets (100 mg) 206Phenytoin Sodium Tablets (100 mg) 207Phenytoin Tablets (100 mg) 207Pioglitazone Hydrochloride Tablets (15 mg/30 mg/45 mg) [87] 208Pipemidic Acid Tablets (200 mg) 209Pipobroman Tablets (25 mg) 210Potassium Chloride Tablets (30 mg) [56, 137] 211Pravastatin Sodium Tablets (10 to 40 mg) [48] 212Prazosin Tablets (5 mg) 212Prednisolone Tablets (5 mg) 213Prednisolone Tablets (10 mg) 214Prednisolone Tablets (20 mg) 214Prednisolone Tablets (20 mg) 214Prednisone Tablets (10 mg) 215Probenecid Tablets (500 mg) 215Promethazine Hydrochloride Tablets (10 mg) [107] 216Promethazine Hydrochloride Tablets (25 mg) 217Propranolol Hydrochloride Tablets (10 mg) 217Propranolol Tablets (40 mg) 217Propranolol Hydrochloride Tablets (10 mg) [141] 218Pyrazinamide Tablets (500 mg) 219Pyrazinamide Tablets (500 mg) 219Pyrazinamide Tablets (500 mg) 220Pyridostigmine Bromide Tablets (10 mg) 221Quetiapine Fumarate Tablets (25 mg/100 mg/200 mg) [161] 221Quinapril Hydrochloride Tablets (5 mg/10 mg/20 mg/40 mg) [51] 222Quinine Sulfate Tablets (300 mg) 223Quinolone Antibiotic Tablets (100 mg) 223Rabeprazole Sodium Tablets (20 mg) [109] 224Raloxifene Tablets (60 mg) [100] 225Ranitidine Hydrochloride Tablets (150 mg) 226Ranitidine Tablets (75 mg) 226Ranitidine Tablets (150 mg) [41] 227Ranitidine Tablets (300 mg) 228Rifampicin, Isoniazid, Ethambutol, and Pyridoxine Tablets (300 mg/200 mg/25 mg) 229Rifampicin Tablets (300 mg) 231Rifampicin Tablets (450 mg) 232Risedronate Sodium Tablets (5 mg/30 mg) [188] 233Risperidone Tablets (4 mg) [1050] 234Rofecoxib Tablets (12.5 mg/25 mg/50 mg) [31] 234Rosiglitazone Maleate Tablets (2 mg/4 mg/8 mg) [86] 235Roxithromycin Dispersible Tablets (200 mg) 235Salbutamol Tablets (2 mg) 236Salbutamol Tablets (4 mg) 237

Serratiopeptidase Tablets (10 mg) 237Serratiopeptidase Tablets (10 mg) 238Sertraline Hydrochloride Tablets (25 mg/50 mg/100 mg) [14] 238Sildenafil Tablets (25 mg/50 mg/100 mg) [43] 239Silimarin Tablets (35 mg) 240Simvastatin Tablets (10 mg) [17] 241Simvastatin Tablets (20 mg) 242Spironolactone Tablets (25 mg/50 mg/100 mg)) [130] 242Stalol Hydrochloride Tablets (500 mg) 243Sulfadimidine Tablets (500 mg) 243Sulfamethoxazole and Trimethoprim Tablets (400 mg/80 mg; 800 mg/160 mg; 100 mg/20 mg) ) [106] 244Sulfamethoxazole and Trimethoprim Tablets (400 mg/80 mg) 245Sulfamethoxazole and Trimethoprim Tablets (800 mg/160 mg; 400 mg/80 mg) 245Sulfamethoxazole and Trimethoprim Tablets, Dispersible (800 mg/160 mg) 246Sulfathiazole Tablets (250 mg) 247Sumatriptan Succinate Tablets (25 mg/50 mg) [125] 247Tamoxifen Tablets (10 mg/20 mg) [191] 248Temafloxacin Hydrochloride Tablets (200 mg/300 mg) 249Tenoxicam Tablets (20 mg) 250Terazosin Tablets (1 mg-10 mg) [126] 250Terazosin Tablets (1 mg) 251Terbinafine Tablets (250 mg) 252Terfenadine Tablets (60 mg) 252Tetracycline Tablets (125 mg) 253Tetracycline Tablets (250 mg) 253Tetrazepam Tablets (50 mg) 254Theophylline and Ephedrine Tablets (130 mg/15 mg) 254Theophylline Tablets (100 mg) 254Theophylline Tablets (100 mg) 255Theophylline Tablets CR (200 mg) 255Tibolone Tablets (0.3 mg) 256Ticlopidine Hydrochloride Tablets (250 mg) 256Tolterodine Tablets (1 mg/2 mg) [171] 257Topiramate Tablets (100 mg/200 mg) [189] 257Tosufloxacin Tosylate Tablets (75 mg) 257Trazodone Hydrochloride Tablets (100 mg) [61] 258Triamcinolone Tablets (4 mg) 258Trifluoperazine Tablets (5 mg) 258Tulobuterol Hydrochloride Tablets (1 mg) 259Valacyclovir Hydrochloride Tablets (500 mg/1 g) [144] 259Valdecoxib Tablets (10 mg/20 mg) [148] 260Valproate Sodium Tablets (500 mg) [121] 260Valsartan and Hydrochlorothiazide Tablets (80 mg/12.5 mg: 160 mg/25 mg) [108] 261Venlafaxine Hydrochloride Tablets (25 mg/37.5 mg/50 mg) [53] 262Verapamil Tablets (120 mg) [65] 263Warfarin Tablets (1, 2, 2.5, 3. 4, 5, 6, 7.5. and 10 mg) [59] 264Zolpidem Tartrate Tablets (5 mg/10 mg) [35] 265

AppendixCoating Solutions 267I. Introduction 267II. Hydroxypropyl Methylcellulose (Methocel, HPMC) Aqueous Coatings 268

A. Brite Rose 268B. Cherry Red 268

C. Geranium Rose 269D. Gloss 269E. Red 269F. Moderate Red 269G. Clear 270H. Green 270I. Holberry Red 271J. Sun Orange 271K. Opadry Yellow (Caplets) 271L. Opadry Yellow (Tabs) 272M. Opadry Red 272N. Opadry Green 272O. White Coating 273

III. Hydroxypropyl Methylcellulose Opaque Organic Coating 273A. Brite Green 273B. Red Mahogany 274C. Sun Orange 274D. Dark Red 275E. Deep Yellow 275F Pale Yellow 275G. Scarlet Red 275

IV. Hydroxypropyl Methyl Cellulose-Hydroxypropyl Cellulose (Klucel) Coating 276A. White 276

V. Hydroxypropyl Methylcellulose-Ethylcellulose Coating 276A. Reddish Orange Opaque 276B. Subcoating Solution 277

VI. Hydroxymethyl Cellulose and Hydroxy Cellulose Coating 277A. Blue 277B. Clear (50:50) 277

VII. Hydroxymethyl Cellulose and Ethyl Cellulose Coating 278A. Clear 278

VIII. Polyvinylpyrrolidone Coatings 278A. Subcoating 278B. Kollidon VA64 279C. Kollidon VA 64 and Polyvinyl Alcohol 279D. Kollidon 30 and Shellac 280E. Kollidon VA 64 and Hydroxypropylmethyl Cellulose 280F. Povidone, Ethylcellulose, and Talc 281

IX. Cellulose Acetate Phthalate and Carbowax Coatings 281A. Brite Green 281B. Cherry Red 281C. Clear 282D. Orange 282E. Red Mahogany 282F. Orange 282

X. Sugar Coatings 282A. Basic 282B. Automatic 283C. Manual White 283

XI. Enteric Coatings 284A. Kollicoat and Kollidon Enteric Film Coating 284B. Eudragit Enteric Aqueous 284

1. Brick Red 2842. Yellow 2853. Brown 285

4. Dark Orange 2855. Orange 2866. Dispersed Orange 286

C. Hydroxypropyl Methylcellulose Phthalate Enteric Coating 2861. Clear Enteric 2862. Orchid Pink Opaque 2873. Light Apricot Orange 287

Index 289