PHA 069 Pharmaceutical Manufacturing PDF

PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: __________________________________________...

PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Lesson title: Materials: I. Current Good Manufacturing Practices Notes, Blue Pen, LAS II. Pharmaceutical Ingredients and Excipients References: Lesson Objectives: Remington; The Science and Practice of At the end of the lesson, the students will be able to: Pharmacy. 22nd edition 1. Explain the jargons used in Manufacturing pharmacy; Rowe, Raymond, Sheskey, Paul, Weller, 2. Identify with the tablet and liquid/suspension pharmaceutical excipients; Paul. Handbook of Pharmaceutical 3. Identify the use of the various pharmaceutical excipients. Excipients: 4th edition https://www.britannica.com/technolo gy/pharmaceutical-industry https://emhartglass.com/files/inspect ion/dfin.htm I. Current Good Manufacturing Practices INTRODUCTION The pharmaceutical industry, as a vital segment of the healthcare system, conducts research and manufacturers and markets pharmaceutical and biological products and medical devices used for the acute or chronic treatment and diagnosis of disease. In the Modern era, the pharmaceutical industry has become a large and very complex enterprise. At the end of the 20th century, most of the world’s largest pharmaceutical companies were located in North America, Europe, and Japan; many of the largest were multinational, having research, manufacturing, and sales taking place in multiple countries. Since pharmaceuticals can be quite profitable, many countries are trying to develop the infrastructure necessary for drug companies in their countries to become larger and to compete on a worldwide scale. The industry has also come to be characterized by outsourcing. That is, many companies contract with specialty manufacturers or research firms to carry out parts of the drug development process for them. Others try to retain most of the processes within their own company. Since the pharmaceutical industry is driven largely by profits and competition—each company striving to be the first to find cures for specific diseases—it is anticipated that the industry will continue to change and evolve over time. What is Drug manufacturing? Drug manufacturing is the process of industrial-scale synthesis of pharmaceutical drugs as part of the pharmaceutical industry. The process of drug manufacturing can be broken down into a series of unit operations, such as milling, granulation, coating, tablet pressing, and others. Terms Used in Manufacturing Pharmacy Actual Yield. The quality that is actually produced at any phase of production of a particular drug based on the initial input. Active Ingredient or Active. Any component which is intended to furnish pharmacological activity or other effects on the diagnosis, cure, mitigation, treatment or prevention of disease, or to effect the structure or function of the body. Batch. A quantity of drug product/device that is homogeneous in character and quality produced during a given cycle of manufacturing and from a specific manufacturing order. Batch Number. A designation of number or letter or combination thereof that identifies the batch and permits the tracing of the complete history if batch, including all stages of its production, control and distribution. (Also known as Lot Number) Bulk Product. Any processed material which has to undergo another process including packaging operation to become a finished product. This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Component. Any material intended to be used for the manufacturer of a product, whether raw materials or packaging materials. Cosmetics. According to Food, Drug and Cosmetics Act, the term is defined as: (1) articles intended to be rubbed, poured, sprinkled, or otherwise applied to the human body or any part thereof, for cleansing, beautifying, promoting attractiveness, or altering the appearance. (2) articles intended or used as a component of any such articles, except that such term shall not include soap. Date of manufacture. The date indicating the start of processing of every batch. Dispensing. The activity of weighing, counting, or measuring and checking of starting materials and issuing these materials to the appropriate production personnel, details of the activity being duly and properly documented. Drug Product. Any substance or mixture of substances finished dosage forms that are manufactured, offered for sale or presented for use in: (1) the treatment, mitigation, cure, prevention, or diagnosis of disease, abnormal physical state or the symptoms thereof in man or animal; (2) the restoration, correction or modification of organic functions in man or animal whether it is in package form. Device. Instrument, apparatus or contrivances, including their components, parts and accessories intended: (1) for use in the diagnosis, cure, mitigation or prevention of disease in man and animals; (2) to affect the structure or any function of the body of man or animal. Expiration Date. A date fixed for each individual batch on or before which the batch is expected to meet the standard specifications for quality, safety and efficacy. Finished Product. A product which has undergone all stages of manufacturing operations. Good Manufacturing Practices (GMP) It is the system of quality assurance aimed at ensuring that products are consistently manufactured to a quality appropriate for their intended use. It is thus concerned with both manufacturing and quality control processes and procedures. In-Process Control. Checks and tests instituted and carried out in the course of the manufacture of a drug to ensure identity, strength, quality and purity. Intermediate Product. Any processed substance or mixture of substances which have to undergo one or more states of processing to become finished product. Lot. A batch or any portion of a batch produced by a continuous process, an amount of drugs produced in a unit of time, or quantity in a manner that ensures its uniformity and in either case is identified by a distinctive lot number and has a uniform character and quality within specified limits. Manufacture or Manufacturing. The complete set of activities to produce a drug, comprising production and quality control from dispensing of materials to the distribution of the finished product. Manufacture Order (MO). It is an instruction to the Production or Manufacturing Department to produce a drug distribution. This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Master Formula (MF). The standard form where the Manufacturing Order is derived. It is prepared by the competent people of the company. Packaging. The process of packing, the part of the production cycle applied to a bulk product to obtain finished product. Packaging Material. Any material used in the packaging of a bulk product to obtain a finished product. Procedures. Description of the operations to be executed, the precautions to be implemented directly or indirectly related to the manufacture of a drug. Processing. The part of the production cycle from weighing of raw materials to finished product. Production. All operations starting from dispensing materials to processing, packaging, to a finished product. Quality Control. All control measures designed to ensure that finished products consistently condor, to established specification of identity, purity, strength and quality. Quarantine. An act of holding off a material for use, or a product for packaging or distribution by physically setting it apart or by a system duly validated, pending a decision on release or rejection. Raw Material. All substances whether active or excipients that are employed in the processing of a finished product. Rejected. The status of materials or products which are not permitted to be used for processing, packaging or distribution. Released or Passed. The status of materials or products which are permitted to be used for processing, packaging or distribution. Representative Sample. A sample representing the lot, the batch, or the total amount of materials based on a sampling plan. Returned Product. Any finished product which is already in distribution and sent back to the manufacturer or distributor due to a complaint, damage, expiration, validity, or other reasons such as the condition of the container or package which may cast doubt on the product identity, quality, strength and safety. Starting Materials. Raw materials used in the production Theoretical Yield. The quantity that is expected or planned to be obtained at any phase of production based on the quantity of components. II. Pharmaceutical Ingredients and Excipients Role of key Tablet Excipients Diluents (fillers and bulking agents) Disintegrants Binders Lubricants Glidants Role of key Liquid/Suspension Excipients Solvents / co – solvents Antifoaming agents Buffering agents Thickening agents Preservatives Sweetening agents Antioxidants Flavouring agents Wetting agents Humectants This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Drug products contain both drug substance (API) and excipients. The resultant biological, chemical, and physical properties of the drug product are directly affected by the excipients chosen, their concentration and interactions with the API: Consistency of drug release Stability including protection from degradation Ease of administration Excipients are subdivided into various functional classifications, depending on the role that they are intended to play in the resultant formulation. Certain excipients can have different functional roles in different formulation types, e.g, lactose, widely used as: A diluent, filler or bulking agent in tablets and capsules A carrier for dry powder inhalation products In addition, individual excipients can have different grades, types and sources depending on those different functional roles. For example, there are various grades of lactose commercially available that have different physical properties, e.g, flow characteristics and particle size distribution. This permits selection of what is considered the most suitable grade for particular need, e.g. with tablet development: - Wet granulation: usually finer grades of lactose are utilized as the binder is utilized more efficiently and this permits better mixing and granule quality - Direct compression: in contrast here, spray dried lactose is used as it flows better and is more compressible In tablets, the key excipient types include: Diluents – lactose, microcrystalline cellulose Disintegrants – sodium starch glycolate, croscarmellose sodium Binders – PVP, HPMC Lubricants – magnesium stearate Glidants – colloidal SO2 Tablet diluents (fillers) Bulking agents – used to make a tablet weight practical for the patient: minimum tablet weight is typically ~50mg. actual API doses can be as low as ~20μg (ex. For oral steroids) Compression aid – deforms and/or fragments readily to facilitate robust bonding in tablet compacts(ex. Microcrystalline cellulose) Good bulk powder flow … diluents have a strong influence – good flow of bulk powders is very important in designing a robust commercial tablet product. Lactose can exhibit poor flow characteristics, so often combined with microcrystalline cellulose in wet granulation tablets, or is used as a better – flowing spray dried version, particularly with direct compression formulations. Disintegrants Disintegrants are added to a formulation to promote the drug release. They do this by increased water wicking into the plug, and they promote deaggregation of the plug particles. For IR tablets disintegrants are essential, but for capsules, they are less important because the plug is less of a barrier to the drug release than a compressed tablet. Tablet binder Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets. Tablet lubricants Tablet lubricants are essential components of all tablet formulations, since they prevent sticking of the tablets in the dies. Lubricants are added to tablet formulations primarily to reduce friction between the die wall and granules as the tablet is formed and ejected This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Tablet glidant A glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability. In tablet manufacture, glidants are usually added just prior to compression. Solvents / Co – solvents Water is the solvent most widely used as a vehicle due to: - Lack of toxicity, physiological compatibility, and good solubilizing power (high dielectric constant), but o Likely to cause instability of hydrolytically unstable drugs o Good vehicle for microbial growth Sorbitol, dextrose, etc, are often added as solubilizers, as well as base sweeteners - Similar pros and cons to water alone Water – miscible co solvents are used to: - Enhance solubility, taste, anti – microbial effectiveness or stability - Reduce dose volume (ex. Oral injections) - Or conversely, optimize insolubility (if taste of API is an issue) - Examples: propylene glycol, glycerol, ethanol, low molecular weight PEGs Water – immiscible co solvents - Emulsions / microemulsions using fractionated coconut oils Buffering agents Can be necessary to maintain pH of the formulation to: - Ensure physiological compatibility - Maintaining or optimizing chemical stability - Maintaining or optimizing anti – microbial effectiveness - Optimize solubility ( or insolubility if taste is an issue) o But optimum pH for chemical stability, preservative effectiveness and solubility may not be the same ▪ Compromises need to be made Preservatives A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by undesirable chemical changes. Antioxidants Antioxidants are substances that may protect your cells against free radicals, which may play a role in heart disease, cancer and other diseases. Free radicals are molecules produced when your body breaks down food or when you're exposed to tobacco smoke or radiation. Efficacy can be affected by: o Compatibility with other excipients o Partitioning into micelles o Adsorption onto surfaces o Incompatibilities (ex. With metal ions) Wetting agents Wetting agents increase the spreading and penetrating properties of a liquid by lowering its surface tension. The surface tension of a liquid is the tendency of the molecules to adhere to each other at the surface, and is determined by the strength of the bonds or attraction between the liquid molecules. Antifoaming agents A defoamer or an anti-foaming agent is a chemical additive that reduces and hinders the formation of foam in industrial process liquids. The terms anti-foam agent and defoamer are often used interchangeably. Strictly speaking, defoamers eliminate existing foam and anti-foamers prevent the formation of further foam. A typical example is simethicone This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Thickening agents This category includes starches as arrowroot, cornstarch, katakuri starch, potato starch, sago, wheat flour, almond flour, tapioca and their starch derivatives. Microbial and Vegetable gums used as food thickeners include alginin, guar gum, locust bean gum, and xanthan gum. Sweetener Sweeteners act as seasoners for fresh vegetables, canned meat products, and seafood. Seasoning action was manifested as enhancement of total flavor, blending of flavor notes, replacement or intensification of sweetness, reductions of bitterness, sourness, and saltiness, and control of flavor factors of rawness. Flavouring agents Flavouring agents are key food additives with hundreds of varieties like fruit, nut, seafood, spice blends, vegetables and wine which are natural flavouring agents. Besides natural flavours there are chemical flavours that imitate natural flavours. Humectants Humectants are ingredients found in lotions and cleansers that hydrate the skin by attracting water molecules like a magnet. Chemically speaking, humectants are hygroscopic substances that form hydrogen bonds with water molecules. This bonding helps moisturize the skin by drawing water from the lower cell layers. Their function is to retard evaporation of aqueous vehicle of dosage form: o To prevent drying of the product after application to skin o Prevent drying of product from the container after first opening o To prevent cap – locking caused by condensation onto neck of container – closure of a container after first opening Table of Pharmaceutical Excipients with its Uses and Concentration CONCENTRATION EXCIPIENT USE/S (%) Lactic Acid Injections 0.012-1.16 Topical preparations 0.015-6.6 Sweetening agent Lactitol Tablet and capsule diluents Therapeutic agent Directly Compressible tablet excipient Lactose, Anhydrous Dry powder inhaler carrier Lyophilization aid Tablet and capsule diluent Tablet and capsule filler Lactose, Inhalation Diluent Dry powder inhaler carrier Dry powder inhaler carrier Lactose, Monohydrate Lyophilization aid Tablet binder Tablet and capsule diluents Tablet and capsule filler Lactose, Monohydrate and Corn Directly compressible tablet excipient Starch Disintegrant Tablet and capsule diluent Lactose, Monohydrate and Tablet and capsule diluent Microcrystalline Cellulose Lactose, Monohydrate and Povidone Tablet and capsule diluent Lactose, Monohydrate and Powdered Tablet and capsule diluents Cellulose Lactose, Spray-Dried Directly compressible tablet excipient Tablet and capsule diluents This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Tablet and capsule filler Lanolin Emulsifying agent Ointment base Lanolin, Hydrous Emulsifying agent Ointment base Lanolin, Alcohols Emulsifying agent Ointment base Lauric Acid Emulsifying agent Food additive 0.1 Lecithin 0.059– 0.295 0.3–2.3 0.25–10.0 Leucine Lubricant Linoleic Acid Surfactant Macrogol 15 Hydroxystearate Dissolution enhancer Nonionic surfactant Solubilizing agent Stabilizing agent. Adsorbent 10–50 Magnesium Aluminum Silicate Binding agent 2–10 Disintegrating agent 2–10 Emulsion stabilizer (oral) 1–5 Emulsion Stabilizer (topical) 2–5 Suspending agent (oral) 0.5–2.5 Suspending agent (topical) 1–10 Stabilizing agent 0.5–2.5 Viscosity modifier 2–10 Absorbent 0.5–1.0 Magnesium Carbonate Tablet excipient (direct compression) 445 Anticaking agent Magnesium Oxide Emulsifying agent Glidant Tablet Capsule diluent Magnesium Silicate Anticaking agent Glidant Magnesium Stearate Tablet capsule lubricant. Anticaking agent Magnesium Trisilicate Glidant Therapeutic agent Acidulant Malic Acid Antioxidant Buffering agent Chelating agent Flavoring agent Therapeutic agent Coating agent Maltitol Diluent Granulation aid Sweetening agent Maltitol Solution Suspending agent Sweetening agent Maltodextrin Aqueous film-coating 2–10 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Carrier 10–99 Crystallization inhibitor for lozenges and 5–20 syrups 10–50 Osmolarity regulator for solutions 20–80 Spray-drying aid 2–40 Tablet binder (direct compression) 3–10 Tablet binder (wet granulation) Maltol Flavor enhancer Flavoring agent Maltose Sweetening agent Tablet diluent. Diluent Mannitol Plasticizer Sweetening agent Tablet and capsule diluent Therapeutic agent Tonicity agent. Emulsifying agent Medium-chain Triglycerides Solvent Suspending agent Therapeutic agent. Meglumine Organic base Inhalation 0.02–0.05 Oral suspension Oral syrup 0.2–0.4 Menthol Tablets 0.2–0.4 Topical formulations 0.05–10.0 Cosmetic products Toothpaste 0.4 Mouthwash 0.1–2.0 Oral spray 0.3 Methionine Oral Pharmaceutical formulations Parenteral preparations Bulk laxative 5.0–30.0 Creams, gels, and ointments 1.0–5.0 Methylcellulose Emulsifying agent 1.0–5.0 Ophthalmic preparations 0.5–1.0 Suspensions 1.0–2.0 Sustained-release tablet matrix 5.0–75.0 Tablet binder 1.0–5.0 Table coating 0.5–5.0 Tablet disintegrant 2.0–10.0 IM, IV, SC injections(a) 0.065–0.25 Inhalation solutions 0.025–0.07 Intradermal injections 0.1 Methylparaben Nasal solutions 0.03 Ophthalmic preparations(a) 0.015–0.2 Oral solutions and suspensions 0.015–0.2 Rectal preparations 0.1–0.18 Topical preparations 0.02–0.3 Vaginal preparations 0.1–0.18 Ophthalmic ointments 3.0–60.0 Mineral Oil Otic preparations 0 0.5–3.0 Topical emulsions 1.0–32.0 Topical lotions. 1.0–20.0 Topical ointments 0.1–95 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Mineral Oil, Light Ophthalmic ointments 415 Otic preparations 450 Topical emulsions 1.0–20.0 Topical lotions 7.0–16.0 Topical ointments 0.2–23.0 Emollient 3.0–6.0 Mineral Oil and Lanolin Alcohols Emulsifier in w/o creams and lotions 5.0–15.0 Emulsifier in o/w creams and lotions 0.5–6.0 Alkalizing agent Monoethanolamine Emulsifying agent Monosodium glutamate Buffering agent Flavoring agent Monothioglycerol Antimicrobial preservative Antioxidant Emulsifying agent Myristic acid Skin penetrant Tablet and capsule lubricant Emollient Myristyl acohol Emulsion stabilizer Oleaginous vehicle Surfactant Thickening agent viscosity-controlling agent Flavor enhancer Neohesperidin Dihydrochalcone Sweetening agent 1–5 ppm Neotame Flavor enhancer Sweetening agent Nitrogen Aerosol propellant Air displacement Nitrous oxide Aerosol propellant Therapeutic agent Emollient Octyldodecanol Emulsifying agent Lubricant solvent Thickening agent Oleic acid Emulsifying agent Skin penetrant Antifoaming agent Oleyl alcohol Dissolution enhancer Emollient Emulsifying agent Skin penetrant Sustained-release agent Olive oil Oleaginous vehicle Emulsifying agent Palmitic acid Skin penetrant Tablet and capsule lubricant Paraffin Ointment base Stiffening agent Adsorbent Pectin Emulsifying agent Gelling agent Thickening agent Stabilizing agent This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Pentetic Acid Antioxidant 0.1 - 0.3 Copreservative 0.05 Petrolatum Emollient topical creams 10 - 30 Topical emulsions 4 - 25 Topical ointments Up to 100 Petrolatum and Lanolin Alcohols Absorption base component 10.0 - 50.0 Emollient and plasticizer in ointments 5.0 - 50.0 Phenol Disinfectant 5.0 Injections (preservative) 0.5 Local anesthetic 0.5 - 1.0 Mouthwash 1% Coating agent Polydextrose Diluent Granulation aid This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Humectant Tablet binder Tablet filler Viscosity-increasing agent Biodegradable material Poly(DL-lactic acid) Coating agent Controlled-release agent Ointment base Plasticizer Polyethylene glycol Solvent Suppository base Tablet and capsule lubricant Mucoadhesive Polyethylene oxide Coating agent Tablet binder 5–85 Thickening agent Organic Solution 12.5 % Polymethacrylates Granules 98 % Powder 95 % Aqueous Dispersion 30 % Emulsifying agent Polyoxyethylene Alkyl Ethers Penetration enhancer Solubilizing agent Wetting agent Polyoxyethylene Castor Oil Emulsifying agent Derivatives Solubilizing agent Wetting agent Polyoxyethylene Sorbitan Fatty Acid Emulsifying agent 1-15 % Esters Solubilizing agent 1-10% Wetting agent 0.1-3.0 % Auxiliary Emulsifier 0.5-5% Polyoxyethylene Stearates Opthalmic ointment 7% Suppository component 1-10% Tablet lubricant 1-2% Dermal route 10-55% Polyoxylglycerides Nasal route 2-22% Oral route (capsule) 10-99% Sublingual route 10-35% Nasal route 8% Polyvinil Acetate Phthalate Tablet enteric film coating 9-10% Tablet sealant (sugar-coating) 28-29% Emulsions 0.5% Polyvinil Alcohol Opthalmic Preparations 0.25-3.00% Topical lotions 2.5% Potassium Alginate Emulsifying agent Stabilizing agent Thickening agent Potassium Alum Mouthwash 1% Potassium Benzoate Carbonated beverages 0.03-0.08% Food products 0.1% Potassium Bicarbonate Effervescent preparation 25-50% Potassium Chloride Therapeutic agent Tonicity agent This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Potassium Citrate Buffer for solutions 0.3-2.0% Sequestering agent 0.32.0% Potassium Hydroxide Alkalinizing agent Antioxidant 0.1-1.0% Potassium Metabisulfite Antimicrobial preservative 0.5-2.0% Sterilizing agent 1.0-5.0% Potassium Sorbate Antimicrobial preservative 0.1-0.2% Carrier for drugs 10-25 % Povidone Dispensing agent Up to 5% Suspending agent Up to 5% Tablet binder, tablet diluent or coating agent 0.5-5 % Eye drops 2-10 % Acidifying agent Propionic Acid Antimicrobial preservative Antioxidant Esterifying agent Propyl Gallate Antioxidant 0.1 % Propylene Carbonate Gelling agent Solvent Humectant (topicals) ~15 Propylene Glycol Preservative (solutions, semisolids) 15–30 Solvent or cosolvent Aerosol solutions 10–30 Oral solutions 10–25 Parenterals 10–60 Topicals 5–80 Emulsifying agent 0.3–5% Propylene Glycol Alginate Foam stabilizer “ Stabilizing agent “ Suspending agent “ Viscosity increasing agent “ IM, IV, SC injections 0.005–0.2 Propylparaben Inhalation solutions 0.015 Intradermal injections 0.02–0.26 Nasal solutions 0.017 Ophthalmic preparations 0.005–0.01 Oral solutions and suspensions 0.01–0.02 Rectal preparations 0.02–0.01 Topical preparations 0.01–0.6 Vaginal preparations 0.02–0.1 Antimicrobial preservative Propylparaben Sodium Penetration agent Pyrrolidone Plasticizer Solvent Solubilizing agent Raffinose Stabilizing agent Sucrose crystallization modifier Saccharin Sweetening agent (oral) 0.02–0.5% w/w Dental paste/gel 0.12–0.3 Saccharin Sodium IM/IV injections 0.9 Oral solution 0.075–0.6 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Oral syrup 0.04–0.25 Emollient Safflower Oil Oleaginous vehicle Solvent Adsorbent Saponite Emulsifying agent Viscosity-increasing agent Sesame Oil. Oleaginous vehicle Solvent Coating agent Shellac Encapsulating agent Film-forming agent Matrixforming agent Modified-release agent Antifoaming agent Simethicone Tablet diluent Water-repelling agent Antimicrobial preservative Sodium Acetate Buffering agent Flavoring agent Stabilizing agent Capsule diluent 10-80 Sodium Chloride Controlled flocculation of suspensions ≤1 Direct compression tablet diluent 10-80 To produce isotonic solutions in intravenous ≤ 0.9 or ophthalmic preparations Water-soluble tablet lubricant 5-20 Buffering agent 0.3-2.0 Sodium Citrate Dihydrate Injections 0.02-4.0 Ophthalmic solutions 0.1-2.0 Sequestering agent 0.3-2.0 Sodium Cyclamate Sweetening agent Antioxidant Sodium Formaldehyde Sulfoxylate Humectant Sodium Hyaluronate Lubricant Sustained-release agent Sodium Hydroxide Alkalizing agent Buffering agent Antimicrobial preservative Sodium Lactate Buffering agent Emulsifying agent Flavoring agent Humectant Anionic emulsifier, forms self-emulsifying 0.5-2.5 Sodium Lauryl Sulfate bases with fatty alcohols Detergent in medicated shampoos ≈10 Skin cleanser in topical applications 1 Solubilizer in concentrations greater than >0.0025 critical michelle concentration Tablet lubricant 1.0-2.0 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Wetting agent in dentrifices 1.0-2.0 Sodium Metabisulfite Antimicrobial preservative Antioxidant Buffering agent Sodium Phosphate, Dibasic Sequestering agent Buffering agent Sodium Phosphate, Monobasic Emulsifying agent Sequestering agent Sodium Propionate Antimicrobial preservative Sodium Starch Glycolate Tablet and capsule disintegrant Sodium Stearyl Fumarate Tablet and capsule lubricant Antimicrobial preservative Sodium Sulfite Antioxidant Sodium Thiosulfate Antioxidant Sorbic Acid Antimicrobial preservative Emulsifying agent Used alone in water-in-oil emulsions 1-15 Sorbitan Esters (Sorbitan Fatty Acid Used in combination with hydrophilic 1-10 Esters) emulsifiers in oil-in-water emulsions Used to increase the water-holding properties 1-10 of ointments Solubilizing agent For poorly soluble, active constituents in 1-10 lipophilic bases Wetting agent For insoluble, active constituents in lipophilic 0.1-3 bases Humectant 3-15 Sorbitol IM injections 10-25 Moisture control agent in tablets 3-10 Oral solutions 20-35 Oral suspensions 70 Plasticizer for gelatin and cellulose 5-20 Prevention of ‘cap locking’ in syrups and 15-30 elixirs Substitute for glycerin and propylene glycol 25-90 Tablet binder and filler 25-90 Toothpastes 20-60 Topical emulsions 2-18 Soybean Oil Oleaginous vehicle Solvent Tablet and capsule diluent Starch Tablet and capsule disintegrant Tablet binder Thickening agent Diluent (hard gelatin capsules) 5-75 Starch, Pregelatinized Tablet binder (direct compression) 5-20 Tablet binder (wet granulation) 5-10 Tablet disintegrant 5-10 Diluent Starch, Sterilizable Maize Lubricant Diluent (hard gelatin capsules) Tablet binder (direct compression) Tablet binder (wet granulation) Tablet disintegrant This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Starch, Pregelatinized Diluent (hard gelatin capsules) 5–75 Tablet binder (direct compression) 5–20 Tablet binder (wet granulation) 5–10 Tablet disintegrant 5–10 Starch, Sterilizable Maize Diluent Lubricant Stearic Acid Ointments and creams 1–20 Tablet lubricant 1–3 Stearyl Alcohol Stiffening agent Sucralose Sweetening agent Confectionery base Coating agent Sucrose Granulation aid Suspending agent Tablet binder Tablet and capsule diluent Tablet filler Therapeutic agent Viscosity-increasing agent Sweetening agent 2–20% w/w Sucrose Octaacetate Alcohol denaturant Dry binder in tablet formulations 5-20% Sugar, compressible Filler in chewable tablets 20-60% Filler in tablets 20-60% Sweetener in chewable tablets 10-50% Sugar Confectioner’s Sweetening agents in tablets 10-20% Tablet diluent 10-50% Sugar spheres Tablet and capsule diluent 62.5-91.5% Complexing agent Sulfobutylether Diluent Viscosity –increasing agent Sulfur dioxide Antibacterial preservative Antioxidant Sulfuric Acid Acidifying agent 95-98 Diluent Sunflower Oil Emollient Emulsifying agent Solvent Tablet binder Suppository Bases Hard Fat Suppository base Tagatose Sweetening agent Dusting powder 90.0-99.0 Talc Glidant and tablet lubricant 1.0-10.0 Tablet and capsule diluent 5.0-30.0 Acidifying agent Tartaric Acid Flavoring agent Sequestering agent Tetrafluoroethane (HFC) Aerosol Propellant Thaumatin Flavor enhancer Sweetening agent 0.5–3 ppm Thimerosal Antimicrobial preservatives Antiseptic IM, IV, SC injections 0.01 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Ophthalmic solutions 0.001–0.15 Ophthalmic suspensions 0.001–0.004 Otic preparations 0.001–0.01 Topical preparations 0.01 Antioxidant Thymol Antiseptic Cooling agent Disinfectant Flavoring agent Skin penetrant Therapeutic agent Coating agent Titanium Dioxide Opacifier Pigment Tragacanth Suspending agent Viscosity-increasing agent Color adjuvant Trehalose Flavor enhancer Freeze-drying agent Humectant Stabilizing agent Sweetening agent Tablet diluent Thickening agent Humectant Triacetin Plasticizer Solvent Tributyl Citrate Plasticizer Emollient Tricaprylin Lubricant Penetration enhancer Solubilizing agent Solvent Triethanolamine Alkalizing agent Emulsifying agent 2–4% v/v Triethyl Citrate Plasticizer Solvent Emollient Triolein Penetration enhancer Solubilizing agent Solvent Vanillin Flavoring agent Vegetable Oil, Hydrogenated Tablet and capsule lubricant 1–6 Tablet binder Absorption enhancer Vitamin E Polyethylene Glycol Antioxidant Succinate Emulsifying agent Granulation aid Ointment base Solubilizing agent Surfactant Suspending agent Tablet binder This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ Water Solvent Up to 100 Emulsifying agent 10% Wax, Anionic Emulsifying Solubilizing agent Stiffening agent Wax, Carnauba Coating agent 10% w/v Cold cream 12.5 Wax, Cetyl Esters Rose water ointment 12.5 Spermaceti ointment 20.0 Topical creams and ointments 1–15 Coating agent Wax, Microcrystalline Controlled-release agent Stiffening agent Emulsifying agent Wax, Nonionic Emulsifying Solubilizing agent Stiffening agent Controlled-release agent Wax, White Stabilizing agent Stiffening agent Controlled release agent Wax, Yellow Polishing agent Stabilizing agent Stiffening agent Xanthan Gum Gelling agent Stabilizing agent Suspending agent Sustained-release agent Viscosity –increasing agent Coating agent Xylitol Diluent Emollient Humectant Sweetening agent Tablet and capsule diluent Tablet filler Zein Tablet coating agent 15 Tablet sealer 20 Wet granulation binder 30 Emollient Zinc Acetate Emulsion stabilizer Gelling agent Opacifier Stabilizing agent Zinc Stearate Tablet Lubricant 0.5-1.5 Water-repellent ointments 2.5 This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ CHECK FOR UNDERSTANDING MULTIPLE CHOICE. Choose the correct answer in the choices provided and write the letter before each number. For items 1 – 5, refer to the following: a. Adsorbent; suspending agent; tablet and capsule diluents; tablet disintegrant b. Emollient; oleaginous vehicle ; solvent c. Gel base; suspending agent; sustained release tablet matrix d. Bioadhesive; emulsifying agent; release – modifying agent; suspending agent; tablet binder; viscosity – increasing agent e. Aerosol propellant; air displacement 1. Carbomer 2. Carbon dioxide 3. Carrageenan 4. Castor oil 5. Cellulose, microcrystalline For 6 – 10, refer to the following: a. Cetyl alcohol d. Dextrose b. Diethanolamine e. Chitosan c. Chlorofluorocarbon 6. Alkalinizing agent; emulsifying agent 7. Coating agent; disintegrant; film-forming agent; mucoadhesive; tablet binder; viscosity – increasing agent 8. Coating agent; emulsifying agent; stiffening agent 9. Aerosol propellants 10. Tablet and capsule diluents; therapeutic agent; tonicity agent; sweetening agent For 11 – 15, refer to the following: a. Ethyl acetate d. Gelatin b. Glycerin e. Ethylcellulose c. Fructose 11. Antimicrobial preservative; emollient; humectants; plasticizer; solvent; sweetening agent; tonicity agent 12. Coating agent; film-former; gelling agent; suspending agent; tablet binder; viscosity – increasing agent 13. Coating agent; flavoring fixative; tablet binder; tablet filler; viscosity – increasing agent 14. Flavoring agent; solvent 15. Dissolution enhancer;flavor enhancer;sweetening agent;tablet diluent For 16 – 20, refer to the following: a. Fumaric acid d. Hexetidine b. Gelatin e. Glycerin c. Hydrochloric acid 16. Clear, colorless, fuming aqueous solution of hydrogen chloride, with a pungent odor 17. Colorless or faint yellow – colored oily liquid with a characteristic amine odor 18. Occurs as a light – amber to faintly yellow – colored, vitreous, brittle solid. It is practically odorless and tasteless and is available as translucent sheets and granules, or as powder. 19. Occurs as white, odorless, or nearly odorless, granules or as a crystalline powder that is virtually nonhygroscopic 20. Clear, colorless, odorless, viscous, hygroscopic liquid; it has a sweet taste, approximately 0.6 times as sweet as sucrose This document is the property of PHINMA EDUCATION  PHA 069: Pharmaceutical Manufacturing with Quality Assurance and cGMP Laboratory Activity Sheet 1 Name: ________________________________________________ Class number: ____ Section: ____________ Schedule: _________________________ Date: _____________ For 21 – 25, refer to the following: a. Lanolin d. Lactose b. Kaolin e. Isopropyl alcohol c. Lactic acid 21. Emulsifying agent; ointment base 22. Diluents for dry – powder inhalers; tablet and capsule diluents 23. Acidifying agent; acidulant 24. Disinfectant ; solvent 25. Adsorbent; suspending agent; tablet and capsule diluents For 26 – 30, refer to the following: a. Lecithin d. Attapulgite b. Cresol e. Acacia c. Cottonseed oil 26. Emollient ; emulsifying agent; solubilizing agent 27. Antimicrobial preservative; disinfectant 28. Oleaginous vehicle; solvent 29. Emulsifying agent; stabilizing agent; suspending agent; tablet binder; viscosity – increasing agent 30. Adsorbent Work Tracker: You are done with this session! Let’s track your progress. Shade the session number you just completed. P1 P2 1 2 3 4 5 6 7 8 9 10 This document is the property of PHINMA EDUCATION