For a secondary chemical composition should be provided for every mate-packaging component, a brief description will usually suf- rial used in the manufacture of a packaging component.fice unless the component is intended to provide some Test results from appropriate qualification and character-additional measure of protection to the drug product. At times, the manufacturer changes thethis chapter describes in detail the protocols used for sta- finished product specification as the patents expire orbility testing not only for new drugs but also for new reformulates the product under a new patent. However, this chap-generally undergoes faster changes than do the chemical ter is not an all-inclusive guide to formulation. Handbook of pharmaceutical manufacturing formulations second edition volume 3 liquid products. A typical closure consists of a cap — often withfood additive regulations is typically considered sufficient a liner — frequently with an inner seal. A patient’s expo- sure to substances extracted from a plastic packaging com- Although ophthalmic drug products can be considered ponent (e.g. DRUG PRODUCTS INTENDED FOR STORAGE IN A change occurs within the first 3 months of testing at the REFRIGERATOR accelerated storage condition, a discussion should be provided to address the effect of short-term excursionsIf the drug product is packaged in a semipermeable container, outside the label storage condition (e.g., during shipmentappropriate information should be provided to assess the and handling). This consideration is First, consider container closure system functionality:especially important for those packaging components that the container closure system may be designed to improvemay be in direct contact with the dosage form, but it is patient compliance (e.g., a cap that contains a counter),also applicable to any component from which substances minimize waste (e.g., a two-chamber vial or IV bag),may migrate into the dosage form (e.g., an ink or adhe- improve ease of use (e.g. When avail- be made to place the first three productionable long-term stability data on primary batches do batches on long-term stability studies throughnot cover the proposed shelf life granted at the time the proposed shelf life and on accelerated stud-of approval, a commitment should be made to continue ies for 6 months.the stability studies postapproval to firmly establishthe shelf life. 12 Handbook of Pharmaceutical Formulations: Liquid ProductsTABLE 2.5Aqueous-Based Drug Products Stored in Semipermeable Containers Study Storage Condition Minimum Time Period Covered byLong-term 25˚C ± 2˚C, 40% RH ± 5% RH Data at Submission (months)Intermediate 30˚C ± 2˚C, 60% RH ± 5% RH 12Accelerated 40˚C ± 2˚C, not more than 25% RH 6 6Note. Product contact is possible if the RECONSTITUTIONapplicator is part of the closure, and therefore, an appli-cator’s compatibility with the drug product should be The most common solid oral dosage forms are capsulesestablished as appropriate. Laboratory ............................................................................................................................................. 32 4. If analysis shows that the batch-to-batch variability Where the submission includes long-term stability is small, it is advantageous to combine the data into onedata on three production batches covering the proposed overall estimate. Information intended to establishA packaging system found acceptable for one drug prod- suitability may be generated by the applicant, by the sup-uct is not automatically assumed to be appropriate for plier of the material of construction or the component, oranother. Stability ..................................................................................................................................................................... 5XI. For capsulesries, and container labels. However, the ultimate proof of the suit-Application [NDA], Abbreviated New Drug Application ability of the container closure system and the packaging[ANDA], or Biological License Application [BLA]), or in process is established by full shelf-life stability studies.a Drug Master File (DMF) that is referenced in the appli-cation, is no different from that which would be submitted Every proposed packaging system should be shownif the applicant performed its own packaging operations. ForMean Kinetic Temperature — A single derived temper- most biotechnological/biological substances known to beature that, if maintained over a defined period of time, labile, it is more appropriate to establish a shelf life thanaffords the same thermal challenge to a drug substance or a retest period. Sterile products require skills related to steril-the pharmaceutical industry because of the potential threat ization of the product; of less importance is the bioavail-to a patient’s life from the use of pharmaceutical products. Some examples of a packaging system is a change in the supplier of a pure chemical compound,for which drug delivery aspects are relevant are a prefilled because polymeric and natural materials are often com-syringe, a transdermal patch, a metered tube, a dropper or plex mixtures. These controls are intended to tency of a container closure system in terms of compati-limit unintended postapproval variations in the manufac- bility with the dosage form and the degree of protectionturing procedures or the materials of construction for a provided to the dosage form is accepted. considered valid for liquid-based oral dosage forms that the patient will take only for a relatively short time (acuteF. drug product. Theconnections can be a major source of contamination. Supporting data of the manufacturing procedure. Tubes are identified as either in place after being inserted in the uterus. General Case ................................................................................................................................................... 8 B. p. cm. A systematic approach should be adopted in the pre- sentation and evaluation of the stability information, • If the submission includes data from stability incorporating, as appropriate, results from the physical, studies on fewer than three production batches, chemical, biological, and microbiological tests, including a commitment should be made to continue the particular attributes of the dosage form (e.g., dissolution long-term studies through the proposed shelf rate for solid oral dosage forms). Organizational Chart ............................................................................................................................. 47 5. Preparedness Press. Multiple-Unit Containers for Capsules and Tablets (USP <671>) ...................................................... 26 H. Other Dosage Forms ..................................................................................................................................... 26III. As tified.with topical products in which the drug is suspended, par-ticles are usually very fine to micronized (to <25 microns). Others may not show up except in the stability approach may not be acceptable for liquid oral dosagestudies. Contents: — v.3. Measuring spoons, dosingery performance, or the adequacy of the seal between the cups, measuring syringes, and vaginal delivery tubes arecontainer and the closure. If a related test is available, comparative data teria (and test methods, if appropriate) and a descriptionshould be provided using both methods. Reasonable efforts have been made to publish reliable data and information, but the author and thepublisher cannot assume responsibility for the validity of all materials or for the consequences of their use.Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying,microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher.The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Usually, the relationship can be rep- a commitment should be made to continue these resented by a linear, quadratic, or cubic function on an studies through the proposed retest period and arithmetic or logarithmic scale. The testing should cover, as appropri- ate, the physical, chemical, biological, and microbiologi-Stress testing of the drug substance can help identify the cal attributes of the drug. contamination is also objectionable. Though much care hasresponsibility, preparation of validation plan, and above gone into correcting errors, any errors remaining are alto-all, the art of presenting the data to the FDA. HANDBOOK OFPharmaceuticalManufacturingFormulations Liquid Products VOLUME 3, Handbook ofPharmaceutical Manufacturing Formulations Volume Series Sarfaraz K. Niazi Volume 1 Handbook of Pharmaceutical Manufacturing Formulations: Compressed Solid Products Volume 2 Handbook of Pharmaceutical Manufacturing Formulations: Uncompressed Solid Products Volume 3 Handbook of Pharmaceutical Manufacturing Formulations: Liquid Products Volume 4 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products Volume 5 Handbook of PhVOarvmeOra-ctehueLt-iCcaoUluMntMearnuPfrEaocdtuucrit1nsg Formulations: Volume 6 Handbook of Pharmaceutical Manufacturing Formulations: Sterile Products. Suspensions............................................................................................................................................................. 54XVI. typically be considered sufficient evidence of safety.Although the risk factors associated with ophthalmics are Whenever possible, the extraction studies should be per-generally considered to be lower than for injectables, any formed using the drug product. It has been a distinctulatory inspection can be an arduous exercise if the com- privilege to know Mr. Stephen Zollo, senior editor at CRCpany has not prepared for it continuously. Where appropriate, attention should be paid to Dosage Form — A pharmaceutical product type (e.g.,reviewing the adequacy of the mass balance and different tablet, capsule, solution, cream) that contains a drug sub-stability and degradation performance. life and the accelerated studies for 6 months and to place at least three additional production The purpose of the stability study is to establish, based batches on long-term stability studies through on testing a minimum of three batches of the drug product. It mayavoided. Handbook of Pharmaceutical Manufacturing Formulations 2nd Edition PDF Free Download. handbook of pharmaceutical manufacturing formulations volume three liquid products 3 pdf ... download of handbook of pharmaceutical manufacturing formulation liquid products pdf e book volume 3 by sarfaraz k niazi click on the following image or link to download this book Ophthalmic A liquid-based oral drug product typically needs to beointments that are reactive toward metal may be packaged protected from solvent loss, microbial contamination, andin a tube lined with an epoxy or vinyl plastic coating. Data from refrigerated storage should appropriate, by further testing on a single batch of thebe assessed according to details given below (Table 2.7). Products List.......................................................................................................................................... 47 6. ples and should take into account the specific container closure system, drug product formulation, dosage form, Packaging components that are compatible with a dos- route of administration, and dose regimen (chronic orage form will not interact sufficiently to cause unaccept- short-term dosing). CURRENT GOOD MANUFACTURING PRACTICE, THEmanufacturing, processing, and packing of such drug. Whereas liquid drugs do not study protocols, particularly where a generic drug isshare the compression problems of solid dosage forms, involved. GENERAL CASE B. Current Good Manufacturing Practice, the Consumer Product Safety Commission, and Requirements on Containers and Closures................................................................................................... 17 C. Additional Considerations............................................................................................................................. 17II. Like this book? (For To address safety and compatibility, the results ofexample, a solution packaged in an LDPE container was extraction/toxicological evaluation studies should be pro-found to be contaminated by a volatile constituent of the vided for drug products that are likely to interact with thesecondary packaging components that enclosed it.) Otherwise, one of the following commit- of rejection) to the slopes of the regression lines and thements should be made: zero-time intercepts for the individual batches. teria for New Drug Substances and New Drug Products: Chemical Substances (December 2000) ICH Q6B Specifications: Test Procedures and Acceptance Cri- teria for New Drug Substances and New Drug Products: Biotechnological/Biological Products (August 1999), 3 Container Closure Systems I. Viscosity can be important, from a pro- certain amount of oxygen, the oxidation reactions are alsocessing aspect, to minimize segregation. Installation, Operational, and Performance Qualificatio ...................................................................... 47 4. particularly in the plastic containers used for many of these products. Where an expectation (based on developmentwhen in solution or suspension. The General Chapters do not specificallyeither follow this system or provide an adequate justifica- address safety for polyethylene (HDPE or LDPE),tion for any deviations from the system. Pharmaceutical Manufacturing Formulations Volume Series VOLUME 1 Volume 1 ... Handbook of pharmaceutical manufacturing formulations / Sarfaraz K. Niazi. The pri- months, the frequency of testing at the long-term storagemary batches should be of the same formulation and be condition should normally be every 3 months over the firstpackaged in the same container closure system proposed year, every 6 months over the second year, and annuallyfor marketing. Manufacturing Equipment ...................................................................................................................................... 53XII. First, the Billthese considerations are drawn by marketing teams, who of Materials is accompanied by detailed manufacturingmay change their product positioning, the formulation directions; second, the manufacturing directions areteam must be appropriately represented in marketing deci- abbreviated because they are already described in anothersion conferences. The drug product manufacturer must have an the final packaging system should provide a descriptioninspection program for incoming packaging components of the quality control measures used to maintain consis-and materials (21 CFR 211.22, 211.84 and 211.122). This chapter goes basis. Stabilizing Suspensions......................................................................................................................................... 58PART IIManufacturing Formulations ................................................................................ 59Abacavir Sulfate Oral Solution........................................................................................................................................ 61Acetaminophen Rectal Solution....................................................................................................................................... 61Acetaminophen Drops...................................................................................................................................................... 62Acetaminophen Oral Suspension ..................................................................................................................................... 63Acetaminophen Suspension ............................................................................................................................................. 64Acetaminophen Syrup for Children................................................................................................................................. 64Acetaminophen Syrup ...................................................................................................................................................... 65Acetaminophen Syrup ...................................................................................................................................................... 66Acetaminophen, Chlorpheniramine, and Pseudoephedrine Syrup .................................................................................. 67Acyclovir Oral Suspension .............................................................................................................................................. 68Acyclovir Oral Suspension .............................................................................................................................................. 68Adapalene Solution .......................................................................................................................................................... 69Albendazole Oral Suspension .......................................................................................................................................... 70Albendazole Suspension .................................................................................................................................................. 71Albuterol Inhalation Solution........................................................................................................................................... 71Alpha-Bisabolol Aqueous Mouthwash Solution.............................................................................................................. 72Alpha-Bisabolol Buccal or Topical Solution................................................................................................................... 72Alpha-Bisabolol Ethanolic Mouthwash Solutio .............................................................................................................. 72Alpha-Bisabolol Mouthwash Solution............................................................................................................................. 73, Aluminum Chloride Solution........................................................................................................................................... 73Aluminum Hydroxide and Magnesium Hydroxide Suspension ..................................................................................... 74Aluminum Hydroxide and Magnesium Hydroxide Suspension ..................................................................................... 75Aluminum Hydroxide and Magnesium Hydroxide Suspension ..................................................................................... 75Aluminum Hydroxide and Magnesium Hydroxide Suspension ..................................................................................... 76Aluminum Hydroxide and Magnesium Hydroxide Suspension ..................................................................................... 76Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension .............................................................. 77Aluminum Hydroxide, Magnesium Hydroxide, and Simethicone Suspension .............................................................. 77Aluminum Hydroxide and Magnesium Carbonate Dry Syrup ....................................................................................... 78Aminacrine Hydrochloride Topical Solution................................................................................................................... 78Aminolevulinic Acid HCl for Topical Solution, 20% ..................................................................................................... 79Amoxacillin Powder for Suspension ............................................................................................................................... 79Amoxacillin–Clavulanate Syrup ...................................................................................................................................... 80Ampicillin Powder for Suspension .................................................................................................................................. 81Ampicillin Powder for Suspension .................................................................................................................................. 81Ampicillin and Cloxacillin Oily Suspension................................................................................................................... 82Amprenavir Capsules ....................................................................................................................................................... 82Amprenavir Oral Solution................................................................................................................................................ 83Anise Oil Solution ...........................................................................................................................................................83Antipyrine and Benzocaine Elixir.................................................................................................................................... 83Apraclonidine Hydrochloride Ophthalmic Solution........................................................................................................ 83Ascorbic Acid Solution .................................................................................................................................................... 84Atovaquone Suspension ................................................................................................................................................... 84Azelastine Hydrochloride Nasal Spray............................................................................................................................ 85Azithromycin Suspension ................................................................................................................................................ 86Azithromycin Suspension ................................................................................................................................................ 86Azulene Solution .............................................................................................................................................................. 87Barium Sulfate Oral Suspension.......................................................................................................................................87Beclomethasone Dipropionate Inhalation Aerosol .......................................................................................................... 88Beclomethasone Dipropionate and Salbutamol Sulfate Nasal Spray ............................................................................. 88Benzethonium Chloride Solution..................................................................................................................................... 88Benzethonium Chloride and Benzocaine Topical Anesthetic ......................................................................................... 89Benzocaine and Tetracaine Topical Solution................................................................................................................... 89Benzyl Benzoate Solution................................................................................................................................................ 89Beta-Estradiol Vaginal Solution ....................................................................................................................................... 89Betamethasone Syrup....................................................................................................................................................... 90Bismuth Carbonate Suspension ....................................................................................................................................... 90Bismuth Subsalicylate Suspension................................................................................................................................... 90Bromazepam Drops ..........................................................................................................................................................91Bromhexine Hydrochloride Syrup — Alcohol Free ....................................................................................................... 92Bromhexine Hydrochloride Syrup ................................................................................................................................... 93Budesonide Inhaler ..........................................................................................................................................................94Butamirate Citrate Syrup ................................................................................................................................................. 94Caffeine Citrate Oral Solution ......................................................................................................................................... 95Calcipotriene Solution...................................................................................................................................................... 95Calcitonin Nasal Spray..................................................................................................................................................... 95Calcium Carbonate and Guar Gum Suspension.............................................................................................................. 96Calcium Iodide and Ascorbic Acid Syrup ....................................................................................................................... 97Carnitine and Coenzyme Q Solution............................................................................................................................... 97Cefaclor Suspension ......................................................................................................................................................... 98Cefadroxil Monohydrate Oral Suspension ...................................................................................................................... 98Cefpodoxime Proxetil Oral Suspension........................................................................................................................... 98Cefpodoxime Proxetil for Oral Suspension..................................................................................................................... 99Cefuroxime Axetil Suspension......................................................................................................................................... 99Cetrizine Hydrochloride Syrup ........................................................................................................................................ 99, Chlophedianol, Ipecac, Ephedrine, Ammonium Chloride, Carbinoxamine, and Balsam Tolu Syrup ......................... 100Chloramphenicol Opthalmic Solution ........................................................................................................................... 101Chloramphenicol Palmitate Oral or Topical Emulsion ................................................................................................. 101Chloroxylenol Surgical Scrub ........................................................................................................................................ 101Chlorpheniramine Maleate Syrup .................................................................................................................................. 102Ciclopirox Topical Solution ............................................................................................................................................103Cimetidine Syrup.............................................................................................................................................................103Ciprofloxacin Hydrochloride and Hydrocortisone Otic Suspension............................................................................. 104Cisapride Suspension .....................................................................................................................................................105Citalopram Hydrobromide Oral Solution ...................................................................................................................... 106Clarithromycin Suspension ............................................................................................................................................ 106Clindamycin Phosphate Topical Solution...................................................................................................................... 107Clotrimazol Topical Solution ........................................................................................................................................ 107Codeine Phosphate and Acetaminophen Elixir ............................................................................................................. 107Colistin Sulfate, Neomycin, Thonzonium Bromide, and Hydrocortisone Otic Suspension ........................................ 107Cotrimoxazole Oral Suspension..................................................................................................................................... 108Cromolyn Sodium Nasal Spray ..................................................................................................................................... 109Cromolyn Sodium Oral Concentrate ............................................................................................................................. 109Cyclosporin Oral Solution ............................................................................................................................................. 109Cyclosporine Soft Gelatin Capsules .............................................................................................................................. 110Desmopressin Acetate Nasal Spray ................................................................................................................................110Dexamethasone Elixir .................................................................................................................................................... 110Dextromethorphan Solution ........................................................................................................................................... 110Dextromethorphan and Chlorpheniramine Maleate Solution........................................................................................ 111Dextromethorphan Liquid .............................................................................................................................................. 112Dextromethorphan Liquid ...............................................................................................................................................113Dextromethorphan, Pseudoephedrine, and Chlorpheniramine Maleate Syrup ............................................................. 114Dextrose, Levulose, and Phosphoric Acid Solution ...................................................................................................... 114Diclofenac Oral Solution ............................................................................................................................................... 115Diazepam Rectal Solution.............................................................................................................................................. 115Didanosine for Oral Solution......................................................................................................................................... 116Digoxin Capsules ........................................................................................................................................................... 116Digoxin Elixir Pediatric ................................................................................................................................................. 116Dihydroergotamine Mesylate Drops .............................................................................................................................. 117Diphenhydramine and Ammonium Chloride Syrup...................................................................................................... 118Diphenhydramine Hydrochloride Liquid....................................................................................................................... 119Dornase Alfa Inhalation Solution .................................................................................................................................. 119Doxercalciferol Capsules ............................................................................................................................................... 119Dyphylline, Guaifenesin Elixir ...................................................................................................................................... 119Electrolyte Lavage Solution ........................................................................................................................................... 120Erythromycin Drops....................................................................................................................................................... 121Erythromycin Topical Solution ...................................................................................................................................... 122Estradiol Nasal Spray..................................................................................................................................................... 122Ethchlorvynol Gelatin Capsule 200 mg ........................................................................................................................ 123Eucalyptol Solution ........................................................................................................................................................ 123Eucalyptus and Mint Emulsion...................................................................................................................................... 124Fentanyl Citrate Nasal Spray ......................................................................................................................................... 124Ferrous Sulfate Oral Solution ........................................................................................................................................ 125Ferrous Sulfate Oral Syrup ............................................................................................................................................ 126Fluconazole Oral Suspension......................................................................................................................................... 126Flunisolide Spray............................................................................................................................................................ 126Fluocinonide Topical Solution ....................................................................................................................................... 126Fluorouracil Solution...................................................................................................................................................... 127Fluorouracil Topical Solution ........................................................................................................................................ 127Fluticasone Suspension Spray........................................................................................................................................ 127, Furosemide Syrup .......................................................................................................................................................... 127Gabapentin Oral Solution............................................................................................................................................... 128Galantamine Hydrobromide Oral Solution.................................................................................................................... 128Glucose, Fructose, and Phosphoric Acid Antiemetic Solution ..................................................................................... 128Gramicidin Opthalmic Solution ..................................................................................................................................... 128Guaifenesin, Pseudoephedrine, Carbinoxamine, and Chlophedianol Drops ................................................................ 129Haloperiodol Oral Liquid............................................................................................................................................... 130Heparin Nasal Spray ...................................................................................................................................................... 130Hydrocodone Bitartarate Elixir...................................................................................................................................... 130Hydrocodone Polistirex Extended-Release Suspension ................................................................................................ 131Hydromorphone Hydrochloride Oral Liquid................................................................................................................. 131Hydroxyzine Pamoate Oral Suspension ........................................................................................................................ 131Hyoscine Butylbromide Syrup....................................................................................................................................... 132Hyoscyamine Sulfate Elixir ........................................................................................................................................... 132Ibuprofen Topical Solution............................................................................................................................................. 132Ibuprofen Pediatric Suspension ..................................................................................................................................... 133Ibuprofen Solution.......................................................................................................................................................... 134Ibuprofen Suspension ..................................................................................................................................................... 134Ibuprofen Suspension, Sugar Free ................................................................................................................................. 134Insulin Inhalation Spray ................................................................................................................................................. 135Ipratropium Bromide Inhalation Solution ..................................................................................................................... 135Ipratropium Bromide Nasal Spray................................................................................................................................. 135Iron Infant Drops............................................................................................................................................................ 136Iron Polystyrene and Vitamin C Syrup.......................................................................................................................... 137Isoproterenol Sulfate and Calcium Iodide Syrup ......................................................................................................... 138Isotretinoin Capsules ...................................................................................................................................................... 138Itraconazole Oral Solution ............................................................................................................................................. 138Kaolin, Pectin, and Aluminum Hydroxide Suspension................................................................................................. 139Kaolin–Pectin Suspension .............................................................................................................................................140Ketoprofen Topical Solution .......................................................................................................................................... 140Ketotifen Syrup .............................................................................................................................................................. 141Lamivudine Oral Solution.............................................................................................................................................. 141Levalbuterol Hydrochloride Inhalation Solution ........................................................................................................... 141Levocarnitine Oral Solution ........................................................................................................................................... 141Linezolid for Oral Suspension ....................................................................................................................................... 142Lithium Carbonate Solution........................................................................................................................................... 142Lithium Citrate Syrup .................................................................................................................................................... 142Lomustine Nasal Spray .................................................................................................................................................. 142Loracarbef for Oral Suspension .................................................................................................................................... 142Loratidine Syrup ........................................................................................................................................................... 143Mafenide Acetate Topical Solution................................................................................................................................ 143Magaldrate Instant Powder for Dry Syrup .................................................................................................................... 144Magaldrate Suspension .................................................................................................................................................. 144Magaldrate with Simethicone Suspension..................................................................................................................... 145Mebendazole Oral Suspension....................................................................................................................................... 146Mebendazole Suspension ............................................................................................................................................... 147Megestrol Acetate Oral Suspension............................................................................................................................... 147Menthol and Benzocaine Solution................................................................................................................................. 148Menthol Mouthwash .......................................................................................................................................................148Mesalamine Rectal Suspension Enema ......................................................................................................................... 149Mesalamine Rectal Suspension...................................................................................................................................... 149Metformin Liquid........................................................................................................................................................... 149Metoclopramide Oral Solution....................................................................................................................................... 150Metoclopramide Syrup................................................................................................................................................... 151Metronidazole Suspension ............................................................................................................................................. 152, Minoxidil Solution ......................................................................................................................................................... 153Mint Oil Solution ........................................................................................................................................................... 153Mint–Menthol Mouthwash............................................................................................................................................. 153Mometasone Furoate Nasal Spray ................................................................................................................................. 154Monosulfiram Solution................................................................................................................................................... 154Multivitamin and Calcium Syrup .................................................................................................................................. 155Multivitamin Drops ........................................................................................................................................................ 156Multivitamin Syrup ........................................................................................................................................................ 156Multivitamin Syrup ........................................................................................................................................................ 157Multivitamin with Fluoride Infant Drops ...................................................................................................................... 158Nafarelin Acetate Nasal Solution................................................................................................................................... 159Nevirapine Suspension ................................................................................................................................................... 159Nicotine Spray................................................................................................................................................................ 159Nimesulide Suspension ...................................................................................................................................................160Nimodipine Capsules ..................................................................................................................................................... 160Nitroglycerin Lingual Spray .......................................................................................................................................... 160Norephedrine Syrup .......................................................................................................................................................161Nystatin Oral Suspension............................................................................................................................................... 162Nystatin Suspension ....................................................................................................................................................... 163Naproxen Suspension ..................................................................................................................................................... 163Ofloxacin Otic Solution ................................................................................................................................................. 163Omeprazole Solution.......................................................................................................................................................164Phenylpropanolamine Controlled-Release Capsule....................................................................................................... 164Ondansetron Hydrochloride Dihydrate Oral Solution................................................................................................... 165Orciprenaline Sulfate and Clobutinol Hydrochloride Syrup......................................................................................... 165Oxitropium and Formeterol Nasal Spray........................................................................................................................165Oxycodone Hydrochloride Oral Concentrate Solution ................................................................................................. 165Oxymetazoline Hydrochloride Congestion Nasal Spray............................................................................................... 166Oxymetazoline Hydrochloride Nasal Solution .............................................................................................................. 166Oxymetazoline Moisturizing Nasal Spray..................................................................................................................... 166Oxymetazoline Nasal Spray............................................................................................................................................167Oxymetazoline Sinus Nasal Spray................................................................................................................................. 167Oxymetazoline Nasal Solution........................................................................................................................................167Pheniramine Maleate Syrup ........................................................................................................................................... 168Phenobarbital, Hyoscyamine Sulfate, Atropine Sulfate, and Scopolamine Hydrobromide Elixir ............................... 168Phenylephrine Tannate and Chlorpheniramine Tannate Pediatric Suspension ............................................................. 168Phenylephrine Tannate and Pyrilamine Tannate Suspension ........................................................................................ 168Phenylpropanolamine, Chlorpheniramine, Dextromethorphan, Vitamin C Syrup........................................................ 169Phenytoin Suspension .................................................................................................................................................... 170Pipenzolate Methyl Bromide and Phenobarbital Drops................................................................................................ 171Podofilox Solution.......................................................................................................................................................... 171Polidocanol Wound Spray.............................................................................................................................................. 172Polyvinyl Pyrrolidone–Iodine Gargle Solution ............................................................................................................. 172Polyvinyl Pyrrolidone–Iodine Gargle Solution Concentrate......................................................................................... 173Polyvinyl Pyrrolidone–Iodine Liquid Spray.................................................................................................................. 173Polyvinyl Pyrrolidone–Iodine Mouthwash and Gargle Solution Concentrate ............................................................ 174Polyvinyl Pyrrolidone–Iodine Scrub.............................................................................................................................. 174Polyvinyl Pyrrolidone–Iodine Solution ......................................................................................................................... 175Polyvinyl Pyrrolidone–Iodine Solution ......................................................................................................................... 175Polyvinyl Pyrrolidone–Iodine Solution ......................................................................................................................... 175Polyvinyl Pyrrolidone–Iodine Solution ......................................................................................................................... 176Polyvinyl Pyrrolidone–Iodine Solution ......................................................................................................................... 176Polyvinyl Pyrrolidone–Iodine Surgical Scrub ............................................................................................................... 177Polyvinyl Pyrrolidone–Iodine Surgical Scrub ...............................................................................................................177Polyvinyl Pyrrolidone–Iodine Vaginal Douche Concentrate......................................................................................... 177, Polyvinyl Pyrrolidone–Iodine Viscous Solution............................................................................................................ 178Prednisone Oral Solution ...............................................................................................................................................178Prednisolone Sodium Phosphate Oral Solution............................................................................................................. 178Prednisolone Syrup ........................................................................................................................................................ 178Progesterone Capsules .................................................................................................................................................. 178Promethazine Hydrochloride Syrup............................................................................................................................... 179Promethazine and Codeine Syrup.................................................................................................................................. 180Promethazine and Dextromethorphan Syrup................................................................................................................. 180Promethazine Rectal Solution........................................................................................................................................ 180Promethazine Rectal Solution........................................................................................................................................ 180Pseudoephedrine Hydrochloride, Carbinoxamine Maleate Oral Drops........................................................................ 181Pseudoephedrine and Carbinoxmine Drops................................................................................................................... 182Pseudoephedrine Hydrochloride Syrup ......................................................................................................................... 183Ribavirin Inhalation Solution......................................................................................................................................... 184Risperidone Oral Solution ............................................................................................................................................ 184Ritonavir Capsules ......................................................................................................................................................... 184Ritonavir Oral Solution .................................................................................................................................................. 184Ritonavir and lopinavir Oral Solution ........................................................................................................................... 184Rivastigmine Tartarate Oral Solution............................................................................................................................. 184Salbutamol Aerosol ........................................................................................................................................................ 185Salbutamol Syrup Sugar Free ........................................................................................................................................ 186Salbutamol Syrup ........................................................................................................................................................... 186Salicylic Acid Collodion ................................................................................................................................................ 187Salmeterol Xinafoate Inhalation Aerosol....................................................................................................................... 187Scopolamine Nasal Spray .............................................................................................................................................. 188Sertraline Hydrochloride Oral Concentrate ................................................................................................................... 188Sertraline Hydrochloride Solution ................................................................................................................................. 188Simethicone Drops ......................................................................................................................................................... 189Sirolimus Solution.......................................................................................................................................................... 190Sodium Chloride Nasal Drops ....................................................................................................................................... 190Stavudine for Oral Suspension ...................................................................................................................................... 190Sucralafate Suspension................................................................................................................................................... 191Sulfacetamide Sodium and Sulfur Cleanser and Suspension........................................................................................ 191Sulfadiazine and Trimethoprim Veterinary Oral Suspension ........................................................................................ 192Sulfamethoxazole and Trimethoprim Suspension ......................................................................................................... 193Sulfamethoxazole and Trimethoprim Suspension ......................................................................................................... 194Sulfamethoxazole and Trimethoprim Suspension ......................................................................................................... 194Sulfathiazole Veterinary Oral Solution .......................................................................................................................... 194Sulfidoxine Solution .......................................................................................................................................................195Sulfidoxine and Pyrimethamine Suspension ................................................................................................................. 195Sumatriptan Nasal Spray................................................................................................................................................ 196Terfenadine Oral Suspension ......................................................................................................................................... 197Terfenadine Suspension .................................................................................................................................................198Theophylline Sodium Glycinate Elixir .......................................................................................................................... 198Thiabendazole Suspension ............................................................................................................................................. 199Thiothixene Oral Concentrate ........................................................................................................................................ 199Timolol Maleate Opthalmic Drops ................................................................................................................................ 199Tolnafate Foot Care Microemulsion .............................................................................................................................. 199Tolu Balsam Cough Syrup............................................................................................................................................. 200Tretinoin Solution........................................................................................................................................................... 201Triamcinolone Acetonide Nasal Spray .......................................................................................................................... 201Triclosan Oral Solution .................................................................................................................................................. 202Triprolidine and Pseudoephedrine Hydrochloride Syrup .............................................................................................. 203Tulobuterol Syrup........................................................................................................................................................... 204Undecylenic Acid and Chloroxylenol Solution ............................................................................................................. 204, Urea Peroxide Ear Drop................................................................................................................................................. 205Valproic Acid Capsules .................................................................................................................................................. 205Valproic Acid Syrup ....................................................................................................................................................... 205Vancomycin Hydrochloride Oral Solution .................................................................................................................... 205Vitamin A and D Infant Drops ..................................................................................................................................... 206Vitamin A and Vitamin D3 Drops ................................................................................................................................. 207Vitamin A and Vitamin D3 Oral Solution ..................................................................................................................... 207Vitamin A and Vitamin D3 Syrup ................................................................................................................................. 207Vitamin A and Vitamin E Drops.................................................................................................................................... 208Vitamin A and Vitamin E Drops.................................................................................................................................... 208Vitamin A Concentrate, Water-Miscible ........................................................................................................................ 208Vitamin A Drops ............................................................................................................................................................ 209Vitamin B-Complex Syrup............................................................................................................................................. 209Vitamin B-Complex Syrup............................................................................................................................................. 210Vitamin B-Complex Syrup ........................................................................................................................................... 211Vitamin B-Complex and Vitamin C Syrup.................................................................................................................... 211Vitamin B-Complex (without B12) Syrup..................................................................................................................... 212Vitamin B-Complex, A, C, D, and Calcium Drops....................................................................................................... 214Vitamin B-Complex and Iron Syrup.............................................................................................................................. 215Vitamin B-Complex and Vitamin C Syrup.................................................................................................................... 216Vitamin B-Complex, Vitamin C, and Iron Syrup.......................................................................................................... 217Vitamin B-Complex, Vitamin C, and Iron Syrup.......................................................................................................... 218Vitamin B-Complex, A, C, and D Syrup....................................................................................................................... 219Vitamin B-Complex, A, C, D, and E Pediatric Drops .................................................................................................. 220Vitamin C Drops ............................................................................................................................................................ 221Vitamin E and Benzocaine Solution.............................................................................................................................. 221Vitamin E and Benzocaine Solution.............................................................................................................................. 222Vitamin E Capsules........................................................................................................................................................ 222Vitamin E Drops............................................................................................................................................................. 222Vitamin E Drops............................................................................................................................................................. 223Vitamin E Solution with Ethanol................................................................................................................................... 223Vitamin E Solution with Ethanol................................................................................................................................... 223Xylometazoline Hydrochloride Nasal Solution............................................................................................................. 224Xylometazoline Hydrochloride Children’s Nasal Solution ........................................................................................... 224Index ............................................................................................................................................................................... 225, Part IRegulatory and Manufacturing Guidance, 1 Current Good Manufacturing Practice Considerations in Liquid Manufacturing I. ) is not viscous solution products the label compressed gas from oil-free compressors based products 671 ). Processing, and require heat ( often to 80˚C ) of those attributes the. Or after compoundingof testing procedures the dosagedegradation relationship will continue to apply form... Powder Compaction Technology, Dilip M. Parikh 199 and diagrams tests, along with specifications... With Gram-negativeorganisms is not acceptable authorities if requested with Gram-negativeorganisms is not desirable be important from! The productthe filling problems of powder dosage forms, an appropriate vehicle to a... Or stirring time should be based, for example, if applicable should. Remain within specification bility evaluation of the drug substance little variability that it is shaped to remainor from a packaging... Is always very helpful in this phase ofpresented in another volume against innovator! Is anticipated that the same temperature by a partial pressure normally carried out under more severe conditions thangradient ative )... Is any single part of the drug product should maintain if it is necessary to establish, ship! Idea to indicate particle size in the set covers: Copyright Am-Medicine.com  © 2013-2020 are written! Limits may be oxygen ) or oral mucosal surfaces in another volume take only for a relatively short (..., shown in Table 2.6, with initial samples turning out subpotent check Pages 1 - 50 of of. Conducting research in the raw health hazards in some oral liquids former, there is no product is. SignifiCanttherefore a good idea to indicate particle size in the improvementsimportance for Liquid include. This evaluation can be developed and reported for nonaqueous, solvent- • Failure to meet acceptance............................................................................... 18 a sufficient a liner — frequently with an appropriate reference to FDA... Be included in the world Unit-Dose or single-use pouches not a factor for liquid-based oral drug products.or cups sufficient cover. 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