Pharmaceutical Sciences Notes

NTA Level 6 • Semester 1 • PST06103 Formulation of Capsule Content Pharmaceutical Production • Source Session/Topic 12 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 12: Formulation of Capsule Content Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define formulation • Outline preparation of fill materials for encapsulation • Selection of capsule size • Explain the determination of capsule fill weight and volume Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |15 minutes |Brainstorming |Formulation | | | |Presentation | | |3 |45 minutes |Presentation |Preparation of Fill Materials for | | | | |Encapsulation | |4 |15 minutes |Presentation |Selection of Capsule Size | |4 |30 minutes |Presentation |Determination of Capsule Fill Weight | | | | |and Volume | |5 |05 minutes |Presentation |Key Points | |6 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Formulation (15 minutes) |Activity: Brainstorming (5 minutes) | | | |ASK students to brainstorm on the following question: | | | |What is formulation? | | | |ALLOW few students to respond? | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY and SUMMARISE by using the content below | • Formulation is the process of determining types and quantities of excipients to be mixed with the active ingredient (the drug) to produce a final medicinal product • The word formulation is also used to mean a dosage form • In large scale or small scale preparation of filled hard gelatin capsules is divided into the following general steps; ➢ Developing and preparing formulation ➢ Selection of size of capsules ➢ Filling the capsule shell ➢ Capsule sealing ➢ Cleaning and polishing the filled capsules • Developing and preparing formulation involves determination of processes, types and quantities of ingredients that will be used in forming a mixture (fill material) to be filled into the capsule shells (in the hard or soft gelatin capsules) • Formulation of capsule fill materials employs two major groups of ingredients, the active ingredients and the excipients o The active pharmaceutical ingredients (API) ▪ The amount and type of active ingredients influence capsule size and nature and amount of excipients to used in the formulation ▪ Active ingredients tend to make up to the high percentage of the contents of a capsule compared to tablets o The excipients ▪ Type and amount of excipient mixed with API depends on the type of capsules to be produced (i.e. hard gelatin capsules or soft gelatin capsules) and the nature of the fill materials i.e. solids (powders, granules, pellets, tablets, small capsules), semi solids and liquids (neat liquids, solutions and suspension) • Pharmaceutical processes involved during formulation of capsule fill material may include milling/comminution, blending/mixing, granulation, pelletization and micronization • Size of the capsule to be produced must be considered during formulation of the fill material STEP 3: Preparation of Fill Materials for Encapsulation (45 minutes) Preparation of Dry Powders • Dry powders are filled into hard gelatin capsules. Formulation and preparation of these powders include processes and different substances which promote the release of drug constituents from the hard gelatin capsules o Milling ▪ In order to achieve uniform drug distribution throughout a powder mix, it is advantageous that the density and particle size of the drug and non-drug components are similar. This is achieved by particle size reduction (milling) o Diluents ▪ Generally, hard gelatin capsules are used to encapsulate between 65 mg and 1 gram of powdered materials (drug and diluents required) ▪ If the dose of the drug in a single dose is smaller than 65 mg to produce the proper fill, lactose, microcrystalline cellulose, and pre-gelatinized starch are common diluents used in capsule filling ▪ If the amount of drug is larger enough to fill a capsule completely, a diluents may not be required ▪ Diluents are present in the greatest concentration of all excipients o Lubricants ▪ They are added to prevent adhesion and facilitate the flow of powder in capsule filling machine e.g. Magnesium stearate and talc o Glidants ▪ The powder mixture or granules must be free-flowing to allow passage from the hopper by the addition of a glidant such as 1% silicon dioxide ▪ Lubricants and glidant are used to improve the filling properties o Wetting agents ▪ These are agents added to facilitate wetting (improve water penetration) of the drug substance by gastrointestinal fluid to enhance dissolution and overcome the problem associated with water insoluble lubricants such as magnesium stearate which can delay the dissolution of the drug and its absorption ▪ Sodium lauryl sulphate is a common wetting agent used in capsules o Disintegrants ▪ Produce disruption of the powder mass when the capsule is in contact with body fluids e.g. crospovidone, sodium and starch • Preparation of Granules and Pellets o Granules and pellets are packed in capsules instead of powders to produce modified release patterns o Granules are produced by granulation process and are more irregular than pellets which are spherical and produced by microencapsulation technique • Preparation of Tablets and Capsules o Tablets and small capsules may be encapsulated in hard gelatin capsules o Tablets and capsules can be encapsulated in order to produce special release forms or to separate incompatible ingredients o Small tablets are made and placed inside capsules following addition of small quantity of the powder and filling completed o Additionally, for separation of one ingredient

NTA Level 6 • Semester 1 • PST06103 Filling Hard Gelatin Capsules Pharmaceutical Production • Source Session/Topic 13 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 13: Filling Hard Gelatin Capsules Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Explain the general process for hard gelatin capsule filling • Explain the methods for hard gelatin capsule filling • List types of hard gelatin capsule filling machines • Explain working of hard gelatin capsule filling machines • Explain the sealing of hard gelatin capsules • Explain the process of cleaning hard gelatin capsules after manufacturing • List common problems encountered during hard gelatin capsule production Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Presentation |General Filling Process | |3 |35 minutes |Presentation |Filling Methods | |4 |25 minutes |Presentation |Capsules Filling Machines | |5 |15 minutes |Presentation |Sealing the Capsules | |6 |10 minutes |Presentation |Cleansing and Polishing Process | |7 | |Presentation |Common Problems during Manufacturing | | |10 minutes |Take home |of Capsules | | | |assignment | | |8 |05 minutes |Presentation |Key Points | |9 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: General Filling Process (10 minutes) • Filling of hard gelatin capsule shells involves a working process with the following steps; o Rectification (orientation of the empty capsule shells in same direction) o Separation of caps from the body o Filling the bodies (bench-scale filling or industrial-scale filling) ▪ E.g. Auger filling principle (flat blade auger or crew auger) o Scraping the excess powder o Replacing the caps o Sealing the capsules o Cleaning the outside of the filled capsules STEP 3: Filling Methods (35 minutes) • Powders and granules can be filled by direct or indirect methods o Direct Filling Methods ▪ The Punch Method ▪ This method is used for small scale filling e.g. filling a small number of capsules in a pharmacy ▪ The powder is placed on a clean paper or porcelain plate and formed into a cake ▪ The empty capsule body is punched vertically into the powder cake repeatedly until filled ▪ Feston Capsule Filling ▪ This methods employs a hand operated capsule filling machine ▪ With this method, about 200-2000 capsules can be produced per hour ▪ Empty capsules are placed on a loader tray which is placed on top of the filler unit of the machine ▪ The loader inserts the capsules into the filling unit and is removed and the top plate is lifted to separate the caps from the bodies ▪ The powder is placed on the unit and the capsule bodies are filled ▪ The top plate is returned to the unit and the caps placed on filled capsule bodies o Indirect Filling Methods ▪ Auger-filling Principle (dependent dosing system) ▪ Employs rotating augers mounted in the hopper and allow a constant flow of powder or granules to the capsules at a constant rate (flat bed auger or screw auger) ▪ Amount of powder fed into the body of the capsules depends on the time the capsule body spends under the hopper outlet and auger speed o Slower rotation of the auger increases fill weight o It is a semi-automated operation o The powder is filled by volume (the capsule body measures the powder or granules) o Requires the powder to have good flow properties ▪ Vibration-filling Principle ▪ A perforated resin plate is positioned in the powder and connected to a vibrator ▪ The powder blend is fluidized by vibration of the plate and assists the powder to flow into the bodies through the holes in the resin plate ▪ This is also known as vibration-assisted filling ▪ Piston Tamp Principle (independent dosing system) ▪ In this method, pistons or taming pins lightly compress the individual doses of powders into plugs (also called slugs) and eject the plugs into empty capsule bodies ▪ Dosator ▪ Consists of cylindrical dosing tube fitted with movable piston ▪ Position of the piston is preset to a particular height to define volume of the capsule ▪ Powder enters the open end of dosator and is slightly compressed against the piston into a plug ▪ The capsules are filled based on weight ▪ Dosing disc o Filling is done on the basis of weight o A solid stop brass plate slides down the dosing disc to close the hole o Five sets of pistons compress the powder into cavities to form plugs • Filling of pellets into hard gelatin capsules may be accomplished through; o Double slide method ▪ Pellets flow from pellet magazine to dosing chambers ▪ Dosing slide is closed to separate dosing chamber and pellet magazine ▪ Outlet slides open o Vacuum-assisted method ▪ Dosing tube enters pellet bed ▪ With the help of vacuum, the pellets are sucked into the dosing tube ▪ Excel pellets are scraped off the end of the dosing tube ▪ Dosing tube is lowered and pellets released into capsule body • Filling of tablets into hard gelatin capsule shells o Dosing slide which can accommodate exactly one tablet moves under the tablet feeder o Slider moves over the capsule body where the tablet simply drops into it o If properly filled, the pin dropped into the capsule body will have limited movements, the horizontal bare connected to the in touches a sensor o If not properly filled, the horizontal bar will switch the sensor

NTA Level 6 • Semester 1 • PST06103 Soft Gelatin Capsules Pharmaceutical Production • Source Session/Topic 14 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 14: Soft Gelatin Capsules Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define soft gelatin capsules • Explain the composition of soft gelatin shell • List the advantages and disadvantages of soft gelatin capsules • Explain the formulation of fill materials for soft gelatin capsules • Explain the filling process for soft gelatin capsules • Explain packaging of soft gelatin capsules • Differentiate soft gelatin capsules from hard gelatin capsules Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |20 minutes |Presentation |Definition and Shell Composition | |3 |10 minutes |Presentation |Advantages and Disadvantages of Soft | | | | |Gelatin Capsules | |4 |30 minutes |Presentation |Formulation of Fill Materials | |5 |20 minutes |Presentation |Filling Process for Soft Gelatin | | | | |Capsules | |6 |10 minutes |Presentation |Packaging of Soft Gelatin Capsules | |7 | |Small group |Difference between Hard and Soft | | |15 minutes |discussion |Gelatin Capsules | | | |Presentation | | |8 |05 minutes |Presentation |Key Points | |9 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Definition and Shell Composition (20 minutes) • Soft gelatin capsules (softgels) are one piece, hermetically sealed, soft gelatin shells containing a liquid, a suspension or a semisolid • They are also known as soft elastic capsules (SEC) • Soft gelatin capsules are available in round, oval, oblong and tube shapes • Soft gelatine capsules are mainly used for oral, vaginal and rectal administration • Typical soft gels are made up of gelatin, plasticizer, preservatives and materials that impart the desired appearance (colorants and/or opacifiers), and sometimes flavours o Plasticizers ▪ They are materials added to make the softgel shell elastic and pliable, usually accounting for 20-30% ▪ The most common plasticizer used in softgels is glycerol, although sorbitol and propylene glycol are used frequently often in combination with glycerol ▪ The amount and choice of the plasticizer contribute to the hardness of the final product and may even affect its dissolution or disintegration characteristics, as well as its physical and chemical stability ▪ Plasticizers are selected on the basis of their compatibility with the fill formulation, ease of processing, and the desired properties of the final soft gel, including hardness, appearance, handling characteristics and physical stability ▪ One of the most important aspect of soft gel formulation is to ensure that there is minimum interaction or migration between the liquid fill matrix and the soft gel shell ▪ The choice of plasticizer type and concentration is important in ensuring optimum compatibility of the shell with the liquid fill matrix o Water ▪ The other essential component of the soft gel shell is water. Water usually accounts for 30-40 % of the wet gel formulation and its presence is important to ensure proper processing during gel preparation and softgel encapsulation ▪ Following encapsulation, excess water is removed from the softgels through controlled drying ▪ In dry gels the equilibrium water content is typically in the range 5-8% w/w, which represents the proportion of water that is bound to the gelatin in the soft gel shell. ▪ This level of water is important for good physical stability, because in harsh storage conditions softgels will become either too soft and fuse together, or too hard and brittled o Colorants/opacifiers ▪ Colorants (soluble dyes, or insoluble pigments or lakes) and opacifiers are typically used in the wet gel formulation ▪ Colorants can be either synthetic or natural, and are used to impart the desired shell colour for product identification ▪ An opacifier, usually titanium dioxide may be added to produce an opaque shell when the fill formulation is a suspension, or to prevent photo degradation of light-sensitive fill ingredients ▪ Titanium dioxide can either be used alone to produce a white opaque shell or in combination with pigments to produce a coloured opaque shell o Chelating agents ▪ Iron is always present in raw gelatin, excess iron should be removed ▪ Addition of chelating agent prevents reaction of iron with other materials e.g. colours o Preservatives ▪ They are added to prevent from microbial attack e.g. fungi growth ▪ This is important because gelatin is susceptible to microbial attack ▪ Preservatives include methyl paraben STEP 3: Advantages and Disadvantages of Soft Gelatin Capsules (10 minutes) • Advantages of soft gelatin capsules o Improved bioavailability (drug is presented in a solubilised form) o Enhanced drug stability o Liquids can be encapsulated (non aqueous liquids) o Easier to swallow and taste can improve compliance o Convenient to carry o Can be enteric coated for delayed release o Popular for pharmaceutical, cosmetics and nutritional products • Disadvantages of soft gelatin capsules o Require special manufacturing equipment o Stability concerns with highly water soluble compounds and compounds susceptible to hydrolysis o Efflorescent materials cannot be encapsulated o Deliquescent materials cannot be encapsulated as they will cause hardening or brittled capsules o Limited choice of excipients/carriers compatible with gelatin STEP 4: Formulation of Fill Materials (30 minutes) • In soft gelatin capsules, the outer shell surrounds a liquid or semi- solid centre (inner fill) o Soft gelatin capsules are suitable for liquids and semisolids • An active ingredient can be incorporated into the outer shell, the inner fill, or both • Formulation of the soft gel capsules

NTA Level 6 • Semester 1 • PST06103 Introduction to Tablets Pharmaceutical Production • Source Session/Topic 15 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 15: Introduction to Tablets Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define tablets • List characteristics of tablets • Classify tablets • List advantages and disadvantages of tablets • List unit processes in tablet manufacturing Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |5 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Buzzing |Definitions | | | |Presentation | | |3 |20 minutes |Presentation |Characteristics of Tablets | |4 |50 minutes |Presentation |Classification of Tablets | |5 | |Small Group |Advantages and Disadvantages of | | |15 minutes |Discussion |Tablets | | | |Presentation | | |6 |10 minutes |Presentation |Unit Processes in Tablet | | | | |Manufacturing | |7 |5 minutes |Presentation |Key Points | |8 |5 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Definitions (10 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |What is a tablet? | | | |ALLOW few pairs to respond and let other pairs to add on points not | |mentioned | | | |WRITE their response on the flip chart/board | | | |CLARIFY and SUMMARIZE by using the content below | • Tablets are defined as compressed or moulded unit solid dosage forms containing one or more medicaments with or without excipients • Tablets are prepared by compressing drugs or mixture of drugs with or without diluents • Tablets differ in ➢ size, ➢ shape, ➢ weight, ➢ hardness, ➢ thickness, ➢ disintegration and ➢ dissolution • characters depending on the amount of medicinal substance and intended mode of administration • Tablets are the most popular dosage forms • Most medicines are available in tablet form except where it is difficult to formulate or administer STEP 3: Characteristics of Tablets (20 minutes) • General characteristics of tablets include the following; o A tablet should have elegant product identity while free of defects like chips, cracks, discoloration, and contamination o Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing o Should have the chemical and physical stability to maintain its physical attributes over time o The tablet must be able to release the medicinal agents in a predictable and reproducible manner o Must have a chemical stability over time so as not to follow alteration of the medicinal agents o Should be uniform in size, weight, and appearance STEP 4: Classification of Tablets (50 minutes) • Tablets can be classified according to the way they are made or mode of administration • Based on how they are made, tablets are classified into; o Compressed tablets ▪ Uncoated ▪ Coated o Moulded tablets ▪ Dispensing tablets ▪ Hypodermic tablets • Based on mode of administration, tablets are classified into; o Tablets ingested orally (oral tablets) ▪ Compressed tablets (CT) e.g. paracetamol tablets ▪ Multiple compressed tablets or press coated tablets ▪ Repeat action tablets ▪ Delayed release tablets e.g. enterically coated bisacodyl tablets ▪ Sugar coated tablets e.g. multivitamin tablets ▪ Film coated tablets e.g. metronidazole tablets ▪ Chewable tablets e.g. antacid tablets o Tablets used in the oral cavity ▪ Buccal tablets ▪ Sublingual tablets ▪ Troches ▪ Lozenges ▪ Dental cones o Tablets administered by other routes ▪ Implantation tablets (implants) ▪ Vaginal tablets e.g. clotrimazole tablets o Tablets to prepare solution ▪ Effervescent tablets e.g. aspirin tablets ▪ Dispensing tablets e.g. enzyme tablets ▪ Hypodermic tablets ▪ Tablet triturates STEP 5: Advantages and Disadvantages of Tablets (15 minutes) |Activity: Small Group Discussion (10 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |What are the advantages and disadvantages of tablets? | | | |ALLOW students to discuss for 10 minutes | | | |ALLOW few groups to present and the rest to add points not mentioned | | | |CLARIFY and SUMMARIZE by using the contents below | • The advantages of tablets over other dosage forms include; o They are unit dosage forms and offer the greatest capabilities of all oral dosage forms for the greatest dose precision and the least content variability o Cost is lowest of all oral dosage forms o Lighter and compact o Easiest to package and strip o Cheapest to package and strip o Easier to swallow o Easy to produce sustainable release product by enteric coating o Objectionable odour and bitter taste can be masked o Suitable for large scale production o Greatest chemical and microbiological stability over all oral dosage forms o Product identification is easy and rapid ▪ By embossing and or monogramming punch face • Disadvantages of tablets include; o Difficult to swallow in case of children and unconscious patients o Some drugs resist compression due to amorphous nature and low density characters ▪ Drugs with poor wetting slow dissolution properties and hence are poorly absorbed from the gastrointestinal tract (hence low bioavailability) ▪ Bitter tasting drugs or drugs with objectionable odour or sensitive to oxygen may require encapsulation or coating, hence increased cost STEP 6: Unit Processes in Tablet Manufacturing (10 minutes) • Formulation of a tablet is governed by a number of factors: o The chemical and physical properties of active ingredient involved and route of administration. o

NTA Level 6 • Semester 1 • PST06103 Formulation of Tablets Pharmaceutical Production • Source Session/Topic 16 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 16: Formulation of Tablets Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define formulation • Explain main ingredients used in tablet production • Classify excipients used in tablet production • List characteristics of excipients used in tablet production • Explain role of excipients used in tablet production Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes|Presentation |Introduction, Learning Tasks | |2 |30 minutes|Presentation |Formulation of Tablets | |3 |25 minutes|Buzzing |Ingredients used in Tablet Production | | | |Presentation | | |4 |50 minutes|Presentation |Classification, Properties and Roles of | | | | |Excipients | |5 |05 minutes|Presentation |Key Points | |6 |05 minutes|Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 1: Formulation of Tablets (30 minutes) • Tablet formulation is the process in which the active pharmaceutical ingredient(s) (APIs) and excipients are combined to produce a tablet o The type and amounts of each ingredient i.e. the medicament(s) and the excipients are known prior to manufacturing process o Formulation must ensure that the dosage form formed is stable acceptable to the patient who will use it o In formulation the variety of ingredients used (including the drug itself) must be compatible with each other o Therefore it is very important to do a lot of formulation studies in order to detect the point of compatibility o Formulation studies must focus on other factors like particle size, polymorphism, pH and solubility, in order to check whether these factors will effect on bioavailability of the drug or not o Oral formulations such as tablets and capsules must be formulated in such as way to ensure that they release the drug(s) in a constant and predictable manner o A formula for tablet production o A formally authorized Master Formula Record or Master Production Record should exist for each product and batch size to be manufactured ▪ This document specifies the starting materials with their quantities and packaging materials, together with a description of the procedures and precautions required to produce a specific quantity of a finished product as well as the processing instructions including the in-process controls STEP 2: Ingredients Used in Tablet Production (25 minutes) • Tablets are composed of two main groups of ingredients; o Active Pharmaceutical Ingredients (APIs) ▪ This is the medicament part of the tablet e.g. paracetamol, diclofenac, amoxicillin etc. ▪ The function of API in tables is to produce pharmacological action upon administration of the tablet o Excipients/Pharmaceutical aids ▪ Excipients or additives are inert materials for the purpose of improving the quality of the tablets or facilitating manufacturing process |Activity: Small Group Discussion ( 10 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |What are the functions of excipients in tablets? | | | |ALLOW students to discuss for 10 minutes | | | |ALLOW few groups to present and the rest to add points not mentioned | | | |CLARIFY and SUMMARIZE by using the contents below | • General functions of excipients are; o Impart weight, accuracy and volume o Ensure accuracy of the dose o Improve solubility o Increase stability o Enhance bioavailability o Modify drug release pattern o Assist product identification o Increase patient acceptability o Facilitate dosage form design STEP 5: Classification, Properties and Roles of Excipients (50 minutes) • Classes of excipients used in the manufacture of tablets include; o Diluents/filler/bulking agents o Binders and adhesives o Disintegrants o Lubricants and glidants o Colouring agents o Flavouring agents o Sweetening agents o Adsorbent • Diluents/filler/bulking agent o They are fillers and make required bulk when the drug(s) is/are not adequate to make the bulk o They also help improve cohesion and permit use of direct compression manufacturing or to promote flow o Some commonly used diluents are Microcrystalline cellulose, Mannitol, Dextrose, Sorbitol, Lactose anhydrous and Starch o Diluents should have the following properties; ▪ Must be non toxic ▪ Must be commercially available in accepted grades ▪ Cost must be low ▪ Must be physiologically inert ▪ Must be physically and chemically stable by themselves and in combination with the drug(s) ▪ Must be free from all microbial contamination ▪ They should not alter the bioavailability of drug ▪ They must be colour compatible • Binders o They are materials added to form granules or to form cohesive compacts for directly compressed tablets o Binders are classified into two groups ▪ Solution binders ▪ Are dissolved in solvent before being added e.g. cellulose, gelatin ▪ Dry binders ▪ These are added to the powder blend e.g. polyethylene glycol (PEG) o Some commonly used binders are acacia, tragacanth, cellulose derivatives (methyl cellulose, hydroxymethyl cellulose, hydroxyproply cellulose), gelatine, glucose, polyvinyl pyrolidone (PVP), starch, sodium alginate, sorbitol • Disintegrants o Are materials added in tablet formulation to facilitate its breaking down when it contacts water in the gastrointestinal tract o They are added before granulation and before compression o Some commonly used disintegrants include starch; starch derivatives (e.g. primogel); clays e.g. veegum, bentonite; cellulose; cellulose derivatives e.g. sodium carboxymethyl cellulose; alginate and polyvinyl pyrolidone cross-linked o Super disintegrants ▪ Swell up to ten times their volume within 30 seconds of contacting water ▪ Examples of super disintegrants include crosscarmellose (cross- linked cellulose), crospovidone, sodium starch glycolate • Lubricants and Glidants

NTA Level 6 • Semester 1 • PST06103 Granulation Pharmaceutical Production • Source Session/Topic 17 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 17: Granulation Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define granulation • List the reasons for granulation • Explain the types of granulation • Explain the process of granulation Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |15 minutes |Presentation |Introduction to Granulation | |3 |25 minutes |Brainstorming |Importance of Granulation | | | |Presentation | | |4 |50 Minutes |Presentation |Granulation Methods | |5 |15 minutes |Presentation |Characteristics of Granules | |6 |05 minutes |Presentation |Key Points | |7 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Introduction to Granulation (15 minutes) Granulation has been defined as “any process whereby small particles are gathered into larger, permanent masses in which the original particles can still be identified • Granulation is a process whereby small (powder) particles are gathered into large permanent masses (granules) in which the original particles can still be identified • It is a process whereby primary powder particles are made to adhere to form larger, multiparticle entities called granules • In granulation process, powder particles are collected together by creating bonds between them through compression or by using a binding agent • Pharmaceutical granules for tablets or capsule production typically have a size range between 0.2 and 0.5 mm depending on their use • Ability to produce reproducible tablets, batch to batch, lot to lot, is directly related to the ability to produce reproducible granulation • Uses of granules; o As dosage form ▪ Where they are packed as bulk granules or divided granules o As intermediate product in preparation tablets ▪ Granules have excellent compressability STEP 3: Importance of Granulation (25 minutes) • Granulation is important for various reasons including; o To prevent segregation of the constituents of powder mix ▪ Segregation is caused by difference is particle size or density of components of the powder mix ▪ The small and/or denser particles concentrate at the base of a container with the larger and/or less denser particles above them ▪ An ideal granulation process will contain all the particles in the mix (smaller or larger and denser or less denser) in the correct proportion in each granule, and thus segregation of ingredients will not occur o To improve flow properties of the mix ▪ Because of small size, irregular shape or surface characteristics, many powders are cohesive and do not flow well ▪ Poor flow will result in weight variation in the final product due variable fill of tablet dies or capsule shells, etc ▪ Granules are larger and flow is improved o To improve compaction characteristics of powder mix ▪ Granules are easier to compress than powders. Some powers are difficult to compact even after inclusion of compactable adhesives o To reduce hazards of toxic dust powders ▪ Powders produce dust during handling, and when toxic powders are being handled it is hazardous to the personnel ▪ Production of non friable granules with suitable strength eliminate the problem of dust production o To reduce the hazard of hygroscopic powders adhesion ▪ Materials that are slightly hygroscopic may adhere to form cake if stored as powder ▪ Granulation reduces this problem because granules can absorb moisture while retaining their flowability due to their larger size o To improve storage ▪ Granules are more convenient to store or ship as they occupy less volume per unit weight (granules are denser than powders) STEP 4: Granulation Methods (50 minutes) • There are two main methods for granulation o Wet granulation, which uses liquid in the process o Dry granulation, which does not use any liquid o Granulation by crystallization is a rarely used method in granulation which exploits the presence of crystallization water in the active materials • During granulation process, a number of different excipients are added in addition to the drug (Diluents, disintegrants, adhesives/binders) • Equipment for granulation process are known as granulators o Different types of granulators are employed depending on the process • Wet granulation o It is the most commonly used method o Wet granulation involves wet massing of a mix of dry primary powder particles using a granulating fluid o It involves the formation of granules by aggregating primary powder particle by using a solution (liquid) containing binding agents dissolved in a solvent. The liquid may also be used without adding binding agent ▪ This liquid or the solution of binding agent is known as granulation fluid ▪ Granulating fluid contains a solvent which must be volatile so that it can be removed by drying, and be non-toxic ▪ Solvents commonly used in wet granulation are water, ethanol and isopropanol either alone or in combination • Organic solvents are used when water-sensitive drugs are processed • Water is used when water-stable drugs are processed. ▪ Advantages of water include non flammability and economical ▪ Disadvantages of using water include ▪ Water may affect stability of the drug e.g. causing hydrolysis ▪ Needs longer drying time than volatile solvents o Granulation fluid ensures particles adhere together once the granule is formed and dried o Steps in wet granulation ➢ Dry mixing (of powder particles) ➢ Wet mixing (addition of granulating fluid) to form a wet mass ➢ Squeezing the wet mass through a sieve to produce wet ribbons ➢ Drying the ribbons ➢ Milling to produce granules of suitable size

NTA Level 6 • Semester 1 • PST06103 Compression Pharmaceutical Production • Source Session/Topic 18 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 18: Compression Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define compression • Explain the importance of pre-compression mixing • List equipments used for tablet pressing • Explain the events during compression • Explain problems encountered in tablet production Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |20 minutes |Presentation |Compression and Pre-Compression | | | | |Mixing | |3 |35 Minutes |Presentation |Equipment Used for Compression | |4 |25 Minutes |Presentation |The Compression Cycle | |5 | |Small group |Problems occurring in Compression | | |25 minutes |discussion | | | | |Presentation | | |6 |05 minutes |Presentation |Key Points | |7 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Compression and Pre-Compression Mixing (20 minutes) • Compression is a unit process in pharmaceutical production in which granules (obtained from granulation) or powder mix are compressed to form tablets • Compression is done after preparation of granules or mixing of ingredients (in case of direct compression) o The granules or powder mix are compressed to form tablets • Compression is accomplished by using equipment called tablet machine or tablet pres • Materials to be compressed into tablets must have good flow properties and compressibility • During compression, the proximity of particles surface causes bond formation between particles which provide coherence to the powder i.e. compact formation • Powder compression causes compaction and consolidation i.e. the increase in mechanical strength of material from particle-particle interactions • Before the granules or powder mix are compressed, pre-compression mixing is done o Excipients such as lubricants, glidants, antiadherents and disintegrants are added in the required proportion onto the surface of granules or powder particles in the powder mix o The reason for pre-compression mixing is to improve tablet manufacturing process e.g. by reducing friction and promoting flow of materials into the compression machine and improve the pharmaceutical quality of the tablets e.g. disintegration • The unit processes in manufacture of tablets are; o Dispensing (weighing) o Granulation (wet or dry) o Drying and sizing o Lubrication o Compression o In-process checking o Packing o Final product analysis and release • In some instances, powder mix is compressed into tablet without passing through granulation process i.e. direct compression • The unit processes in the manufacture of tablets are shown in figure 21.1 below; Figure 21.1: Unit process in tablet manufacturing [pic] STEP 3: Equipment Used for Compression (35 minutes) • After mixing the ingredients, the powder mix or the granules (after pre- compression mixing) are compressed into tablets by using a machine called Tablet Press • There are two types of tablet presses; o Single punch (single station) tablet press ▪ This is for small scale production of tablets o Multi-station (rotary) tablet press ▪ This is for large scale production of tablets • Tablet press o A tablet press is a high speed machine that squeezes (compresses) the ingredients (granules or powder mix) into required tablet shape and size o Tablet presses can also press the name of the manufacturer, of the product or other markings into the top of the tablet o A typical single punch tablet press consists of the following parts; ▪ A hopper shoe • This is for holding and delivering powder mix or granules into the compression chamber in the die ▪ A die • A disc shaped piece of hardened steel with a hole cut up of through its centre • The hole in the die is known as a compression chamber • The functions of the compression chamber; • To receive materials for compression • It is where compression takes place • Provides shape and size to the tablets ▪ A punch (A set of two punches for each die) • It is a rod-shaped hardened steel that fits into top or bottom of the die • For each die, there are two punches (a lower punch –which fits into the bottom of the die and an upper punch –which fits into the top of the die) • The punches press name of the manufacturer, name of the product or other markings into the top of the tablet during compression • The function of the upper punch • To compress the materials in the die chamber (by downward movement) to form a tablet • Functions of the lower punch • Lower punch controls the size of the tablet • Eject the tablet from the die chamber after it is formed ▪ Ejection regulating screw • It controls the movement of the lower punch during ejection of the tablet ▪ Capacity regulating screw • Adjust lower punch movement to control volume of materials into the die chamber • This determines thickness of the tablet o A typical multi-station or rotary tablet press consists of the following sections and parts; ▪ Upper cam section • Consists of the upper compression roller and all adjustment to the position of upper compression rollers • The primary components of the upper cam section are; o Upper punch removal/dwell cam o Upper punch lowering cam o Upper pre-compression and main compression rollers section depth adjustment o Upper punch pull up-cam o Cam material of construction ▪ Compression section • Contains all the components that are exposed to the materials to be compressed • It is

NTA Level 6 • Semester 1 • PST06103 Tablet Coating Pharmaceutical Production • Source Session/Topic 19 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 19: Tablet Coating Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define tablet coating • List reasons for tablet coating • Explain types of tablet coating • Explain equipment for tablet coating Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |10 minutes |Brainstorming |Meaning of Tablet Coating | | | |Presentation | | |3 |15 minutes |Presentation |Reasons for Tablet Coating | |4 |10 minutes |Presentation |Factors Considered in Tablet Coating | |5 |35 Minutes |Presentation |Types of Tablet Coating | |6 |35 Minutes |Presentation |Equipment for Tablet Coating | |7 |05 minutes |Presentation |Key Points | |8 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Meaning of Tablet Coating (10 minutes) |Activity: Brainstorming (5 minutes) | | | |ASK students to brainstorm on the following question: | | | |What is tablet coating? | | | |ALLOW few students to respond | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY and SUMMARISE by using the content below | • Coating is a process by which an essentially dry, outer layer of special material is applied to the surface of a dosage form in order to confer specific benefits over uncoated variety • Tablet coating is the last (optional) critical step in tablet production cycle and one of the oldest pharmaceutical processes still in existence STEP 3: Reasons for Tablet Coating (15 minutes) ➢ Coating masks unpleasant odour, taste or colour of the drug ➢ Coating provides physical and chemical protection for the drug ➢ Coating controls the release of drug from the tablet ➢ Coating protects the drug from gastric environment of stomach in case of acid sensitive drugs ➢ Coating help avoid chemical incompatibility ➢ Coating improves pharmaceutical elegance by using colours and contrasting printing STEP 4: Factors Considered in Tablet Coating (10 minutes) • Tablet properties o Tablet to be coated must possess the proper physical characteristics like spherical shape and uniform surface o Tablets to be coated must be able to tolerate attrition during coating process i.e. tablets must be resistant to abrasion and chipping ▪ for example, tablet surfaces that are brittle and soften in presence of heat or affected by coating composition and tend to become rough in the early stages of coating process are unacceptable for film coating • Coating process o Coating equipment o Coating parameters o Facility and ancillary equipment o Automation of coating process • Coating composition o Polymers, colour, plasticizer and solvent STEP 5: Types of Tablet Coating (35 minutes) • There three types of tablet coating o Sugar coating o Film coating ➢ Non enteric film coating ➢ Enteric film coating o Other types of coating include compression coating, electrostatic coating, DIP coating, vacuum film coating, dry coating and laminated coating • Sugar Coating o Sugar coating involves the application of sugar solution with colour to the tablets for several times to give uniform and elegant film o Tablets suitable for sugar coating are those; ➢ with deep convex surfaces with thin rounded edges ➢ resistant to breakage, chipping and abrasions (sugar coating process is long and vigorous) o Sugar coating involves the following steps; ➢ Sealing ➢ Sub-coating ➢ Syruping (smoothing) ➢ Finishing ➢ Polishing o Sealing Step ▪ This step prevents penetration of moisture into the tablet core ▪ Over wetting tablets during coating causes moisture to penetrate the tablet core and lead to softening or disintegration of the tablet hence affecting physical and chemical stability of the tablet ▪ Materials used for sealing tablets include shellac (more effective but lengthens disintegration and dissolution times), zein (alcohol soluble protein derivative), oleic acid, polyethylene glycol and alcohol methylene chloride o Sub-coating Step ▪ Sub coating is applied to form uniform edges and to build up the tablet size ▪ Sub-coating increases the tablet weight from 50 to 100% ▪ Materials used for sub-coating include gelatin, sugarcane powder, corn syrup, distilled water, gum acacia ▪ This step involves; ▪ Application of binder solution to the tablets ▪ Dusting of the sub-coating with powders and drying until the entire tablets have covered and desired thickness is achieved o Syruping Step ▪ Syruping is done in order to cover the imperfections in the tablet surface caused during sub-coating step ▪ This step involves; ▪ Application of syrup coating with grossing syrups followed by the addition of dilute colorants to provide tinted base ▪ Syrup coating constitute colorants, sub-coating powder, calcium carbonate, cane sugar powder, corn starch, syrup and distilled water ▪ When the tablets are quit smooth, a syrup solution containing dye (colouring agent)e is applied until final size and colour are achieved ▪ Finally a clear syrup coat without dye is applied to the syruped tablets o Polishing Step ▪ Polishing is done to obtain the desired lustre to the tablets ▪ Tablets are polished in standard coating pans by application of carnauba wax (yellow), bees wax (white), paraffin wax or warm solution of waxes in naphtha or suitable volatile solvents o Advantages of sugar coating ➢ It prevents unpleasant odour ➢ Gives sweet taste to the tablet by masking any unpleasant or bitter taste ➢ It is highly elegant and glossed o Disadvantages of sugar coating ➢ Appreciable increase in size of the tablets ➢

NTA Level 6 • Semester 1 • PST06103 Packaging of Tablets and Capsules Pharmaceutical Production • Source Session/Topic 20 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 20: Packaging of Tablets and Capsules Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define packaging • List Materials used in Tablet of Packaging • Explain Types of Packaging Materials for Tablets and Capsules • Describe Procedures for Packaging of Tablets and Capsules Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |25 minutes |Presentation |Introduction to Packaging | |3 |25 Minutes |Brainstorming |Characteristics of Packaging | | | |Presentation |Materials | |4 |40 Minutes |Presentation |Types of Packaging Materials | |5 |15 minutes |Brainstorming |Selection of Packaging Materials | | | |Presentation | | |6 |05 minutes |Presentation |Key Points | |7 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Introduction to Packaging Materials (25 minutes) • Packaging is the science, art and technology of enclosing or protecting a product and providing information about the product for distribution, storage, sale and use • Pharmaceutical packaging is defined as the economical means of providing presentation, protection, identification, information, convenience, compliance, integrity and stability of the product • Packaging for pharmaceutical uses may be glass (type I, type II, type III and type IV), plastic (thermosetting type, thermoplastic type), rubber, paper/cardboards or metals (aluminium, tin plated steel, stainless steel, tin and lead) • Importance of Packaging o Provision of physical protection to products o Facilitates use of the product by patient o Provide dose control o Identifies the product o Helps in transmission of information (lebelling) o Provides integrity of the product o Provide security to the product o Packaging promotes the product ▪ Packaging is a bridge between production and marketing STEP 3: Characteristics of Packaging Materials (25 minutes) |Activity: Brainstorming (5 minutes) | | | |ASK students to brainstorm on the following question: | | | |Mention the characteristics of packaging materials? | | | |ALLOW few students to respond | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY and SUMMARISE by using the content below | • They should protect the product from environmental condition • Should be nonreactive with the product • Should not impart taste or odour to the product • Should be nontoxic • Should be adoptable to commonly high speed packaging equipment • Should meet applicable tamper resistance requirements Requirements of a pharmaceutical packaging are; o Should allow easy of dispensing o Should be child resistant but senior friendly o Should be hemetically sealed o Modularized machinery STEP 4: Types of Packaging (40 minutes) • Packaging materials are grouped into three general classes; primary, secondary and tertiary packaging materials • Primary Packaging o Primary packaging is the material that envelops the product and holds it ▪ Primary packaging are in direct contact with the product ▪ Provides the smallest unit of distribution or use ▪ Examples of primary packaging include aerosol spray can, blister pack and bottles o Blister Packaging ▪ It is a primary packaging materials used for small consumer goods ▪ Blister packs are commonly used for unit dose packaging for tablets and capsules ▪ The principal components of pharmaceutical blister packages; • The forming film (blister) o It is a pocket inside which the product fits o This pocket or cavity in the forming film is used to receive the tablet or the capsule o Forming film accounts for approximately 80-85% of the blister pack o Receives the product in deep drawn pockets o Backing or Lidding material ▪ It is sticked over the back of the blister and makes up 15-20% of the package ▪ Provides the base or main structural component upon which the final blister package is built ▪ The lidding material is sealed onto the support material • After the tablets have been properly fed to the preformed support materials, the lidding material is sealed onto the support material • Temperature for sealing ranges from 140C to 300 C ▪ Materials used for backing/lidding are; • Paper • Paper-aluminium combination • Aluminium foil ▪ The backing or lidding material can be push-through type, peelable type (used to provide child resistant packing), pee-push, tear-open and child resistant options • Formation of a blister pack o Thermosoftening ▪ Involves heat softening a sheet of thermoplastic resin and then vacuum drawing the softened sheet of plastic onto a mould ▪ After cooling the sheet is released from the mould o Filling ▪ The sheet then proceeds to the filling station for filling o Sealing ▪ Sealing is then accomplished by lidding it with a heat sealable backing material o Advantages of blister packaging; ➢ Ensures product integrity ➢ Ensures product protection ➢ Provides tamper evident packaging ➢ Reduces the possibility of accidental misuse ➢ Enhances patient compliance o Strip Package ▪ A strip package is formed by feeding two webs of a heat sealable flexible film through a heated crimping rollers ▪ Strip packaging is used for capsules and tablets ▪ Materials used include; • Foil laminations (for moisture sensitive products) • Paper • Polyethylene • Cellophane (transparent plastic film formed from processed cellulose) ▪ Steps involved in the formation of a strip package; ▪ The product is fed into the pocket formed between two heat sealable flexible films ▪ Sealing is accomplished by heat crimping rollers ▪ The strip is then cut into desired

NTA Level 6 • Semester 1 • PST06103 Quality Assurance and Quality Control Pharmaceutical Production • Source Session/Topic 21 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 21: Quality Assurance and Quality Control Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Explain quality assurance in pharmaceutical manufacturing • Explain quality control in pharmaceutical manufacturing • Differentiate between quality assurance and quality control • Explain quality variations in pharmaceutical manufacturing • Define documentation in pharmaceutical manufacturing • List documents required for pharmaceutical manufacturing • Explain the importance of documentation in pharmaceutical manufacturing Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer • Handout 21.1: Raw Material Quality Assurance Monograph SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |20 minutes |Presentation |Quality Assurance in Pharmaceutical | | | | |Production | |3 |15 minutes |Presentation |Quality Control in Pharmaceutical | | | | |Production | |4 |10 minutes |Presentation |Difference between QA and QC | |5 |30 minutes |Presentation |Quality Variation in Pharmaceutical | | | | |Production | |6 |30 minutes |Presentation |Documentation in Pharmaceutical | | | | |Production | |7 |05 minutes |Presentation |Key Points | |8 |05 minutes |Presentation |Evaluation | SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing STEP 2: Quality Assurance in Pharmaceutical Production (20 minutes) • Quality is the totality of features and characteristics of a medicinal product and its ability to satisfy stated and/ or implied needs o Quality begins with research and development o Quality is designed and built in the product • Quality assurance (QA) is a wide ranging concept covering all matters that individually or collectively influence the quality of a product • QA is a totality of the arrangements to ensure that the drug is continuously of the right quality for the intended use • Quality assurance is a part of quality management focused on providing confidence that quality requirements will be fulfilled • Quality Assurance incorporates GMP (which incorporates QC) and also includes product design and development with special focus on process design o GMP is a part of QA which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use o Quality relationships in a pharmaceutical industry is; Quality Management Quality Assurance Good Manufacturing Practice (GMP) Quality Control • Elements of Quality Assurance circle in Pharmaceutical Manufacturing; o Research o Development o Prototyping o Documentation o Raw materials o Facilities (buildings) o Equipment o Personnel and supervision o Monitoring, feedback, follow-up • Features of a good QA system; o It is a process, not an end point o It must be independent of financial pressures o Must ensure that quality policies are followed o Must have final authority in product acceptance, rejection and release to public o Must be an integral part in production o Must be responsible for day-to-day operations and for longer term goal settings • Responsibilities of QA include the following; o QA department is responsible for ensuring that the quality policies adopted by the company are followed o Helps to identify and prepare the necessary SOPs relative to the control of quality ▪ Ensures that SOPs are prepared, approved, used and updated o It must determine that the products meet all the applicable specifications and that it was manufactured according to the internal standards of GMP o QA is responsible for quality monitoring or audit function o QA functions to assess operations continually and to advise and guide them towards full compliance with all applicable internal and external regulations o Ensures that proper documentation is followed ▪ Documents are systematic and well kept ▪ Quality manuals are made and staff trained and motivated to comply • Primary functions of QA o Quality control (analytical testing of products) o Raw materials control (sampling, inspecting and testing of incoming raw materials) o Packaging and labelling components (bottles, foils, labels, measures, cartons) o Physical inspection of product and operations at critical intermediate stages ▪ In-process quality control ▪ Batch review ▪ Batch release o Management of internal audit system o Handle customers’ feedback and satisfaction o Management of deviations, incidents and investigations o Management of GMP training system o Management of validation system STEP 3: Quality Control in Pharmaceutical Production (15 minutes) • Quality control (QC) is a component of GMP concerned with sampling, specification and testing, documentation and release procedures which ensure that the necessary and relevant tests are performed and the product is released for use only after ascertaining its quality • QC is a part of quality management focused on fulfilling quality requirements • Responsibilities of QC o QC department is responsible for day-to-day control of quality within the company o QC plays major role in selection of qualified vendors from whom raw materials are purchased ▪ Tests representative samples as required ▪ Audit vendor’s operations to determine suitability of the vendor and degree of compliance with GMPs prior to being approved o QC is responsible for analytical testing of incoming raw materials (e.g. assay, titrations etc) o QC is responsible for analytical testing and inspection of packaging components, including labelling (e.g. appearance, spectroscopy, loss on drying etc) o QC is responsible for conducting in-process testing when required, perform environmental monitoring, and inspect operations for compliance o QC is responsible for conducting required tests on finished products or dosage forms (e.g. assay, dissolution, content uniformity etc) o Environmental areas for manufacturing of various dosage forms are tested and inspected by QC department o Generally QC is responsible for efficacy, safety,