Pharmaceutical Manufacturing Formulations

Transcription

1 HANDBOOK OF Pharmaceutical Manufacturing Formulations Uncompressed Solid Products VOLUME 2 Sarfaraz K. Niazi CRC PRESS Boca Raton London New York Washington, D.C.

2 Table of Contents Parti Regulatory and Manufacturing Guidelines 1 Chapter 1 Global Good Manufacturing Practices Compliance 3 I. Introduction 3 A. General Provisions 5 B. Organization and Personnel 5 C. Buildings and Facilities 6 D. Equipment 7 E. Control of Components and Drug Product Containers and Closures 8 F. Production and Process Controls 9 G. Packaging and Labeling Controls 10 H. Holding and Distribution 13 I. Laboratory Controls 13 J. Records and Reports 15 K. Returned and Salvaged Drug Products 18 Chapter 2 Compliance Program Guidance Manual for FDA Staff: Drug Manufacturing Inspections 21 I. Background 21 II. Implementation 21 A. Objectives 21 B. Strategy Biennial Inspection of Manufacturing Sites Inspection of Systems A Scheme of Systems for the Manufacture of Drugs and Drug Products 22 III. Program Management Instructions 23 A. Definitions Surveillance Inspections Compliance Inspections State of Control Drug Process Drug Manufacturing Inspection 24 B. Inspection Planning 24 C. Profiles 24 IV. Inspectional Observations 25 A. Investigational Operations General Inspection Approaches System Inspection Coverage Sampling Inspection Teams Reporting 29 V. Analytical Observations 30 A. Analyzing Laboratories 30

3 B. Analysis 30 VI. Regulatory /Administrative Strategy 30 Chapter 3 Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification 33 I. Introduction 33 II. The Biopharmaceutics Classification System 33 A. Solubility 33 B. Permeability 34 C. Dissolution 34 III. Methodology for Classifying a Drug Substance and for Determining the Dissolution Characteristics of a Drug Product 34 A. Determining Drug Substance Solubility Class 34 B. Determining Drug Substance Permeability Class Pharmacokinetic Studies in Humans Intestinal Permeability Methods Instability in the Gastrointestinal Tract 36 C. Determining Drug Product Dissolution Characteristics and Dissolution Profile Similarity 36 IV. Additional Considerations for Requesting a Biowaiver 37 A. Excipients 37 B. Prodrugs 37 C. Exceptions Narrow Therapeutic Range Drugs Products Designed to Be Absorbed in the Oral Cavity 37 V. Regulatory Applications of the BCS 37 A. INDs/NDAs 37 B. ANDAs 38 C. Postapproval Changes 38 VI. Data to Support a Request for Biowaivers 38 A. Data Supporting High Solubility 38 B. Data Supporting High Permeability 38 C. Data Supporting Rapid and Similar Dissolution 39 D. Additional Information 39 References 39 Appendix A 39 Chapter 4 Guidelines on Formulating Uncompressed Solids 41 I. Relative Humidity 41 II. Surface Area 41 III. Sieve Analysis 41 IV. Particle Size Distribution 42 V. Powder Flow Properties 42 VI. Real, Tapped, and Bulk Density 43 VII. Solid Handling 43 VIII. Mixing of Powders 43 IX. Oral Powders 43 X. Capsules 43 XI. FDA Classification of Capsule Types 44 XII. FDA Classification of Powders 45 XIII. Inhalers and Lung Delivery 45 XIV. Problems in Powder Handling 45

4 XV. Capsulation Equipment 46 XVI. Capsule Finishing 46 XVII. Modified-Release Products 46 XVIII. Clinical Test Supplies and Placebos 46 XIX. Coated Particles 46 XX. Mixing Mechanisms 46 XXI. Segregation Mechanisms 46 XXII. Mixing Equipment 47 XXIII. Milling 47 Part II Uncompressed Solids Formulations 49 Acebutolol Hydrochloride Capsules 51 Aceclofenac Instant Granules 51 Acetaminophen and Diphenhydramine Hydrochloride Hot Therapy Sachet 52 Acetaminophen Capsules 500 mg 52 Acetaminophen, Doxylamine, and Caffeine Effervescent 53 Acetaminophen Instant Granules 54 Acetaminophen, Pseudoephedrine Hydrochloride, Chlorpheniramine Hot Therapy Sachet 55 Acetaminophen, Pseudoephedrine Hydrochloride Hot Therapy Sachet 56 Acetaminophen Swallow Capsules 56 Acetazolamide Sustained-Release Capsules 57 Acetylcysteine Sachets 57 Acitretin Capsules 58 Acrivastine and Pseudoephedrine Hydrochloride Capsules 59 Acyclovir Capsules 59 Adenosine Monophosphate Topical Powder 60 Aluminum Acetate Powder 60 Aluminum Hydroxide and Magnesium Carbonate Dry Syrup 60 Aminosalicylic Acid Granules 61 Amlodipine Besylate and Benazepril Hydrochloride Capsules 61 Amlodipine Besylate Capsules 62 Amoxicillin and Bromhexine Hydrochloride Capsules 62 Amoxicillin and Clavulanic Acid Powder for Suspension, 125 mg and mg per 5 ml 63 Amoxicillin and Clavulanate Potassium for Suspension 64 Amoxicillin Powder for Suspension 125 and 250 mg 65 Amoxicillin Trihydrate Capsules 250 and 500 mg 65 Ampicillin Powder for Suspension 66 Ampicillin Trihydrate Capsules 66 Ampicillin Trihydrate Capsules for Suspension 67 Ampicillin Trihydrate Powder for Suspension 67 Antibacterial and Bacterial Culture Capsules 68 Antifungal Foot Powder 68 Aspartame Granules in Sachet 69 Aspartame Powder in Sachet 69 Aspirin and Chlorpheniramine Powder 69 Aspirin and Phenylpropanolamine Powder 70 Aspirin Microencapsulated Sustained-Release Capsules 70 Aspirin, Salicylamide, and Caffeine Powder 70 Azithromycin Capsules 71 Azithromycin Capsules and Oral Suspension 72 Azithromycin for Oral Suspension "72

5 Azithromycin Sachet for Oral Suspension 73 Balsalazide Disodium Capsules 74 Benazepril Hydrochloride and Amlodipine Besylate Capsules 75 Bisacodyl Colonic Delivery Capsules 76 Brompheniramine and Pseudoephedrine Capsules 76 Budesonide Capsules 77 Budesonide Inhalation Powder 77 Butalbital and Acetaminophen Capsules 77 Calcitonin (Salmon) Capsules 78 Calcitriol Capsules 79 Calcium Carbonate Microencapsulated Sustained-Release Capsules 80 Camptothecin Capsules 80 Carbamazepine Extended-Release Capsules 81 Cefaclor Capsules 82 Cefdinir Capsules and Oral Suspension 82 Cefixime for Oral Suspension 82 Cefpodoxime Proxetil for Oral Suspension 82 Cefprozil for Oral Suspension 83 Ceftibuten Capsules and Oral Suspension 83 Ceftibutin for Oral Suspension 83 Cefuroxime for Oral Suspension 84 Celecoxib Capsules 84 Cellulose Triacetate Liquefiable Topical Powder 85 Cephalexin Capsules 85 Cephalexin Powder for Oral Suspension 86 Cephradine Capsules 86 Cephradine Powder for Suspension 87 Cevimeline Capsules 87 Chlordiazepoxide Hydrochloride Capsules 88 Chloroxylenol and Chlorhexidine Topical Powder 88 Chlorpromazine Sustained-Release Capsules 89 Cimetidine Microencapsulated Sustained-Release Capsules 89 Citrate Effervescent Powder 90 Clindamycin Capsules 150 mg 90 Clofibrate Capsules 91 Clonidine Sustained-Release Capsules 91 Clorazepate Dipotassium Capsules 92 Cyclosporin A Capsules 92 Dantrolene Sodium Capsules 93 Dextroamphetamine Sulfate Capsules 93 Diclofenac and Misoprostol Capsules 93 Diclofenac Sustained-Release Capsules 94 Didanosine Delayed-Release Capsules 95 Didanosine Delayed-Release Capsules Enteric-Coated Beadlets 95 Didanosine for Oral Suspension 95 Diethyl Toluamide Topical Powder 96 Difluoromethylornithine-Alpha Capsules 97 Diltiazem Hydrochloride Extended-Release Capsules 99 Diphenhydramine Hydrochloride Capsules 100 Dipyridamole and Aspirin Extended-Release Capsules 100 Divalproex Sodium Capsules 100 Divalproex Sodium Coated Particle Capsules 100 Dofetilide Capsules 100 Doxepin Hydrochloride Capsules 101 Doxycycline Capsules 101 Doxycycline Hyclate Capsules 101

6 Doxycycline Hydrochloride Capsules and Oral Suspension 102 Efavirenz Capsules 102 Enalapril Maleate Capsules 102 Erythromycin and Bromhexine Powder for Suspension 103 Erythromycin and Sulfisoxazole Granules for Suspension 104 Erythromycin Delayed-Release Capsules 105 Erythromycin Ethylsuccinate for Oral Suspension 106 Erythromycin Ethylsuccinate for Oral Suspension 200 mg/5 ml 107 Erythromycin Stearate for Oral Suspension 108 Erythropoietin Capsules 110 Esomeprazole Magnesium Capsules Ill Estramustine Phosphate Capsules Ill Ethosuximide Capsules 112 Etodolac Capsules 112 Eye Nutrition Supplement Capsules 112 Felbamate for Oral Suspension 112 Fenofibrate Capsules 113 Fexofenadine Hydrochloride Capsules 114 Fluconazole for Oral Suspension 114 Flucytosine Capsules 114 Fluoxetine Capsules 115 Fluoxetine Hydrochloride Capsules 115 Fluoxetine Hydrochloride Instant and Weekly Capsules 116 Flutamide Capsules 116 Fluticasone Propionate and Salmeterol Xinafolate Inhalation Powder 116 Fluvastatin Sodium Capsules 117 Formoterol Fumarate Inhalation Powder 117 Formoterol Fumarate Inhaler Capsules 117 Fosfomycin Tromethamine Sachets 118 Gabapentin Capsules 118 Ganciclovir Capsules 118 Gemfibrozil Capsules 119 Glycoprotein Ila/IIb Capsules 119 Guaifenesin Sustained-Release Capsules 120 Herbal AIDS Treatment Capsules 120 Histadine Capsules 120 Human Growth Hormone Capsules 121 Hydrochlorothiazide and Triamterene Capsules 122 Hydrochlorothiazide Capsules 122 Hydroxyzine Pamoate Capsules and Oral Suspension 122 Hyoscyamine Sulfate Capsules 122 Ibuprofen Microencapsulated Sustained-Release Capsules 123 Ibuprofen Sustained-Release Capsules 124 Ifosfamide Capsules 125 Imatinib Mesylate Capsules 125 Indinavir Sulfate Capsules 126 Indomethacin Capsules 127 Indomethacin Microencapsulated Sustained-Release Capsules 129 Indomethacin Sustained-Release Capsules 130 Insulin Capsules '31 Iron-Polysaccharide Complex Capsules 132 Isometheptene Mucate, Dichloralphenazone, and Acetaminophen Capsules '32 Isosorbide Mononitrate Capsules 20 mg 133 Isradipine Capsules '33 Itraconazole Capsules '34 Ketoprofen and Misoprostol Capsules 134

7 Ketoprofen Capsules 135 Lansoprazole Capsules 135 Lansoprazole Delayed-Release Capsules 135 Lincomycin Capsules 136 Linezolid Oral Suspension 136 Lipase, Amylase, and Protease Capsules 136 Lithium Carbonate Capsules 136 Lopinavir-Ritonavir Capsules 137 Loracarbef Capsules and Oral Suspension 137 Loxapine Capsules 137 Loxapine Succinate Capsules 137 Magaldrate Instant Powder or Dry Syrup 138 Magnesium Oxide Capsules 138 Mefenamic Acid Capsules 138 Mesalamine Capsules 138 Mesalamine Colonic Delivery Capsules 139 Methsuximide Capsules 139 Methylphenidate Capsules 140 Methylphenidate Immediate- and Extended-Release Capsules 140 Methyltestosterone Capsules 141 Metoclopramide Hydrochloride Sustained-Release Capsules 141 Metyrosine Capsules 142 Miconazole Nitrate Foot and Itch Powder 142 Mineral Powder for Topical Herpes Simplex 142 Minocycline Hydrochloride Capsules 142 Mixed Amphetamine Salt Capsules 143 Mixed Amphetamine Salts Enteric-Release Capsules 143 Morphine Sulfate Capsules 144 Morphine Sulfate Controlled-Release Capsules 145 Morphine Sulfate Sustained-Release Capsules 146 Multivitamin Effervescent Granules 147 Multivitamin Instant Granules 148 Mycophenolate Mofetil Capsules and Oral Suspension 148 Nanoparticle Polymer Particle Powders 149 Nelfinavir Mesylate Oral Powder 150 Nilvadipine Capsules 150 Nitrofurantoin Capsules 150 Nitrofurantoin Sustained-Release Capsules 151 Nizatidine Capsules 151 Nystatin Powder 151 Omeprazole and Piroxicam Capsules 152 Omeprazole Capsules 153 Omeprazole Delayed-Release Capsules 153 Oral Rehydration Salt 45 meq 154 Orlistat Capsules 155 Oseltamivir Phosphate Capsules and Oral Suspension 156 Oxcarbazepine Oral Suspension 156 Oxycodone Hydrochloride and Acetaminophen Capsules 156 Oxytetracycline Hydrochloride Capsules 157 Oxytetracycline Hydrochloride, Sulfamethizole, and Phenazopyridine Hydrochloride Capsules 157 Pancrealipase Capsules 157 Pancrealipase Capsules Enteric-Coated Microspheres 158 Penicillamine Capsules 158 Pentosan Polysulfate Sodium Capsules 158 Pentostatin Capsules 158 Phenobarbital and Hyoscyamine Sulfate Capsules 158

8 Phenoxybenzamine Hydrochloride Capsules 159 Phentermine Capsules 159 Phentermine Hydrochloride Capsules 159 Phenytoin Sodium Extended-Release Capsules 159 Piroxicam and Beta-cyclodextrin Topical Powder 160 Piroxicam Capsules 161 Polyethylene Glycol 3350 Powder for Reconstitution 162 Polythiazide Capsules 162 Potassium Chloride Extended-Release Capsules 162 Potassium Chloride for Oral Solution 162 Potassium Chloride Microencapsulated Sustained-Release Capsules 163 Potassium Chloride Powder 20 meq 164 Prazosin and Polythiazide Capsules 164 Prednisolone Targeted-Release Capsules 165 Procarbazine Hydrochloride Capsules 165 Prochlorperazine Sustained-Release Capsules 165 Propoxyphene Hydrochloride, Caffeine, and Aspirin Capsules 166 Propoxyphene Hydrochloride Capsules 166 Propranolol Hydrochloride and Hydrochlorothiazide Capsules 166 Propranolol Hydrochloride Long-Acting Capsules 166 Propranolol Hydrochloride Multiple Bead Capsules 167 Propranolol Hydrochloride Sustained-Release Capsules 169 Propranolol Timed- and Sustained-Release Capsules 170 Pseudoephedrine and Guaifenesin Capsules 170 Pseudoephedrine Hydrochloride Capsules 170 Ranitidine Effervescent Granules 171 Ribavirin Capsules 171 Rifabutin Capsules 171 Rifampicin Capsules 171 Rifampin and Isoniazid Capsules 171 Rivastigmine Tartrate Capsules 172 Salmeterol Xinafolate Capsules 172 Salmeterol Xinafolate Inhalation Powder 172 Saquinavir Mesylate Capsules 172 Selegiline Hydrochloride 173 Sevelamer Hydrochloride Capsules 173 Sibutramine Hydrochloride Capsules 173 Stavudine Capsules '73 Succimer Capsules 174 Sucralafate Granules '74 Tacrine Hydrochloride Capsules 174 Tacrolimus Capsules '75 Talc, Crospovidone, and Starch Topical Powder 175 Tamsulosin Hydrochloride Capsules 176 Temazepam Capsules '77 Temozolomide Capsules '77 Terazosin Hydrochloride Capsules 178 Tetracycline Hydrochloride Capsules '78 Thalidomide Capsules 17^ Theophylline Sustained-Release Capsules 179 Thiothixene Capsules '7 l) Tibolone Capsules 1X() Tiotropium Inhalation Powder l^(l Tolmetin Sodium Capsules lx ' Tolterodine Capsules IX ' Topiramate Capsules ' xl

9 Tretinoin Capsules 182 Triamterene and Hydrochlorothiazide Capsules 182 Triamterene Capsules 182 Triclosan and Zinc Undecylenate Powder 183 Trientine Hydrochloride Capsules 183 Trimethoprim and Sulfamethoxazole Oral Suspension 183 Trimipramine Maleate Capsules 183 Troleandomycin Capsules 184 Typhoid Vaccine Live Oral Capsules 184 Valsartan and Hydrochlorothiazide Capsules 184 Valsartan Capsules 185 Vancomycin Hydrochloride Capsules 185 Verapamil Hydrochloride Capsules 186 Verapamil Hydrochloride Sustained-Release Capsules 187 Vincamine Capsules 188 Vinpocetine Multiple Bead Capsules 189 Vitamin B-Complex, Amino Acids, and Magnesium Effervescent Granules (Sugar-Free) 190 Vitamin B-Complex and Vitamin C Instant Granules 191 Vitamin C and Calcium Carbonate Effervescent Tablets 191 Zanamivir Powder 192 Zidovudine Capsules 192 Zinc Oxide and Cornstarch Powder 192 Ziprasidone Hydrochloride Capsules 193 Zonisamide Capsules 194 Index 195