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NTA Level 6 • Semester 1 • PST06103 Management of Pharmaceutical Wastes Pharmaceutical Production • Source Session/Topic 25 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 25: Management of Pharmaceutical Wastes Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define pharmaceutical wastes • List sources of pharmaceutical wastes • List types of wastes in pharmaceutical production • Explain the problems caused by pharmaceutical wastes • Explain methods used in the disposal of pharmaceutical wastes 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 |Buzzing |Definitions | | | |Presentation | | |3 | |Small group |Sources of Pharmaceutical Wastes | | |35 minutes |discussion | | | | |Presentation | | |4 |30 Minutes |Presentation |Types of wastes produced during | | | | |pharmaceutical production and their | | | | |problems | |5 |30 minutes |Presentation |Disposal of Pharmaceutical wastes | |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: Definitions (10 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |What is a pharmaceutical waste? | | | |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 | • Wastes are unwanted materials which are no longer used in the manufacturing process that can eventually turn into hazardous or non hazardous material to human or the environment or both • Pharmaceutical wastes are wastes are unwanted materials resulting from pharmaceutical production processes • Pharmaceutical wastes are in different forms mainly as expired materials, manufacturing wastes and others STEP 3: Sources of Pharmaceutical Wastes (35 minutes) |Activity: Small Group Discussion (15 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |What are the sources of waste in pharmaceutical manufacturing? | | | |ALLOW students to discuss for 15 minutes | | | |ALLOW few groups to present and the rest to add points not mentioned | | | |CLARIFY and SUMMARIZE by using the contents below | • Manufacturing processes o Wastes generated during pharmaceutical production ▪ by-products from different stages of manufacturing ▪ Spillages ▪ Waste water • Raw materials o Unusable/expired/rejected/obsolete raw materials o Expired/unusable/rejected active pharmaceutical ingredients • Products o Rejected finished products • Packaging materials o Unusable or damaged packaging materials • Quality control laboratories o Used chemical by products o Spills o Unused/unusable solvents, chemicals and reagents o Waste water • Cleaning and maintenance processes o Cleaning substances e.g. detergents, soaps o Waste waster STEP 4: Types of Wastes Produced in Pharmaceutical Production and their Problems (30 minutes) • Pharmaceutical wastes are classified into o Hazardous wastes o Non-hazardous wastes o Hazardous wastes ▪ Hazardous wastes are wastes that are dangerous or potentially harmful to human health or environment ▪ Hazardous wastes can be liquids, solids, gases or sludges ▪ Hazardous wastes exhibit hazardous properties such as: Ignitability ▪ Ignitibility is a property of a pharmaceutical waste to present fire hazard under routine storage, disposal and transportation or are capable of exacerbating a fire once it has started ▪ Ignitable wastes are easily combustible or flammable ▪ Ignitable wastes include flammable liquids and compressed gases Corrositity ▪ Corrosive pharmaceutical wastes are wastes capable or corroding metals or other materials or burn the skin ▪ These have a pH of 2 or lower or 12.5 or higher Reactivity ▪ Reactive wastes are unstable under normal conditions ▪ They undergo violent changes ▪ They can cause explosions, toxic fumes, gases or vapours when heated, compressed, or mixed with water ▪ They include glacial acetic acid, sodium hydroxide etc Toxicity ▪ Wastes that are toxic contain toxic organic chemicals or toxic heavy metals such as chromium, lead, mercury or cadmium Infectivity ▪ Ability of waste to cause infection ▪ These are from microbiological laboratories or from production of vaccines or immunological preparations o Non-hazardous wastes ▪ Non-hazardous pharmaceutical wastes are those wastes that present no significant hazardous properties ▪ These wastes are below the threshold of causing harm to human health • Problems associated with pharmaceutical wastes |Activity: Small Group Discussion (15 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |What are the problems associated with industrial pharmaceutical | |wastes? | | | |ALLOW students to discuss for 15 minutes | | | |ALLOW few groups to present and the rest to add points not mentioned| | | | | |CLARIFY and SUMMARIZE by using the contents below | o Environmental contamination with drug substances ▪ Fumes, dust etc. ▪ Antimicrobial resistance when antimicrobial wastes contaminate the environment STEP 5: Disposal of Pharmaceutical Wastes (30 minutes) • Methods for disposal of pharmaceutical wastes; o Incineration ▪ Incineration is an effective method for disposal of wastes (solid, liquid and gaseous waste), in which solid organic wastes are subjected to combustion so as to convert them into residue and gaseous products (heat, gas, steam and ash) by use of an incinerator ▪ Is useful for disposal of residue of both solid waste management and solid residue from waste water management ▪ Reduces the volumes of

NTA Level 6 • Semester 1 • PST06103 GMP for Pharmaceutical Equipments Pharmaceutical Production • Source Session/Topic 24 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 24: GMP for Pharmaceutical Equipments 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 GMP requirements for equipment used in pharmaceutical manufacturing • Explain the construction features of GMP compliant equipment • Outline the basic equipment used in pharmaceutical production • Explain the calibration of equipment used in pharmaceutical production • Explain the cleaning of equipment used in pharmaceutical production • Explain the preventive maintenance of equipment used in pharmaceutical 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 |Buzzing |General Features of Manufacturing | | | |Presentation |Equipment | |3 | |Small group |GMP Requirements for Equipments | | |35 minutes |discussion | | | | |Presentation | | |4 |20 Minutes |Presentation |Construction of Equipment | |5 |25 minutes |Presentation |Basic Equipment in Pharmaceutical | | | | |Manufacturing | |6 |25 Minutes |Presentation |Calibration, Cleaning and Maintenance| | | | |of Equipment | |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: General Features of Manufacturing Equipment (10 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |What are the features of pharmaceutical manufacturing equipment? | | | |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 | • Equipment used in the manufacture, processing, packing or holding of a drug product must be of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance • Effectiveness of equipment starts at the design stage • Pharmaceutical manufacturing companies contribute indirectly in the design of equipment by providing information on requirements and feedback on existing equipment • Equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out • Equipment should be constructed of materials that suit the operation and use of the equipment for the range of products manufactured and tested on site. • The construction materials should not corrode or deteriorate and thus influence the manufacturing or testing procedure. STEP 3: GMP Requirements for Equipments (35 minutes) |Activity: Small Group Discussion (10 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | | | |What are the GMP requirements for equipment used in pharmaceutical | |production? | | | |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 | • Pharmaceutical manufacturing equipment should meet the following requirements; o Operating criteria ▪ Should be adequate to meet process, size, speed and effectiveness requirements o Spare parts ▪ Availability of spares and servicing ▪ This can result in using different makes of an equipment in different parts of the world o Maintenance ▪ Frequency and ease of maintenance significantly impact on productivity and even quality ▪ Equipment break down during process could adversely affect quality ▪ Cleanability of the equipment ▪ Accessibility to the parts of equipment needed to be cleaned ▪ Easy of disassembling and re-assembling the equipment o Environmental issues ▪ Dust dissemination ▪ Potential for contamination of other products and requiring operators to wear additional protective clothing and frequent cleaning of facility ▪ Noise and energy use o Equipment design, size and space required for its location o Construction materials of the equipment o Process controls on the equipment ▪ Automatic weight adjustment on tablet presses ▪ Temperature recorders on ovens o Cost of the equipment ▪ Base price of the equipment ▪ Additional costs related to installation, etc. o Design and maintenance manuals ▪ Manuals are important for validation/qualification of the equipment and maintenance programs STEP 4: Construction of Equipment (20 minutes) • Equipment layout and design must aim to minimize risks of error and permit effective cleaning and maintenance o This will avoid cross-contamination, dust and dirt-build up and any adverse effect on the quality of the product • Equipment must be installed to minimize risks of error and contamination • The construction of the equipment must meet the following features; o Surfaces ▪ Surfaces that contact components, in-process materials or drug product should be smooth, nonreactive or absorptive ▪ These surfaces should not alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements o Fixed pipework (for transfer of materials through pipelines) ▪ All pipes used must be of right standard and specification for the material and pipeline to prevent any wrong connections and mix- ups ▪ All pipes must be clearly labelled ▪ Labels in all pipes should indicate contents and direction of flow ▪ Servicing pipings and devices must be adequately marked ▪ The use of adaptors is not recommended ▪ Piping system should allow monitoring and testing of materials delivered in them at regular intervals o Substances required for operation of equipment ▪ Coolants, lubricants and other substances required for operation of the equipment

NTA Level 6 • Semester 1 • PST06103 GMP for Pharmaceutical Premises Pharmaceutical Production • Source Session/Topic 23 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 23: GMP for Pharmaceutical Premises 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 concept of GMP on pharmaceutical premises • List the general GMP Requirements on Design of Premises • Explain how pharmaceutical manufacturing premises are maintained Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer 0 SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |20 minutes |Presentation |GMP and Manufacturing Premises | |3 |25 minutes |Presentation |General GMP Requirements on Location | | | | |of Premises | |4 | |Small group |General GMP Requirements on Design of| | |40 Minutes |discussion |Premises | | | |Presentation | | |5 |20 Minutes |Buzzing |Maintenance of Premises | | | |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: GMP and Manufacturing Premises (20 minutes) • Good Manufacturing Practices (GMP) are a part of Quality Assurance (QA) which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use • GMP is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product • GMP covers all aspects of production; o Raw materials o Premises o Equipment o Personnel • Principles of GMP are; o Proper design and construction of premises o Following written procedures and instructions o Documentation of work o Validation of work o Monitoring facilities and equipment o Writing SOPs o Designing, developing and demonstrating job competence o Protection against contamination o Controlling components and product related processes o Conducting planned and periodic audits • The premise for pharmaceutical production must meet the GMP standards STEP 3: General GMP Requirements on Location of Premises (25 minutes) • The land and buildings where the manufacturing operations are located must contribute towards the quality of the products • Proper location and design help avoid the risks of contamination, permitting effective cleaning and maintenance, minimizing the build-up of dirt and dust and preventing quality defects • Premises must be located, designed, constructed, adapted and maintained for production processes to; ➢ Minimize risks of errors and cross-contamination ➢ Permit effective cleaning ➢ Permit effective maintenance ➢ Minimize build-up of dirt and dust ➢ Eliminate any adverse effects on quality • Principle for the location of pharmaceutical production premise; o Location must minimize risks of cross-contamination ▪ Not located next to a melting factory with high airborne levels of yeast o Location must be in conducive climatic and geographic (e.g. away from noise, earthquake hazards, flooding, humidity, ) • A site inspection is useful before building commences to ensure that the area is suitable for the construction of a pharmaceutical factory STEP 4: General GMP Requirements on Design of Premises (40 minutes) |Activity: Small Group Discussion (10 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |What are the GMP requirements on design of premise? | | | |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 | • Premises should be laid out in such a way as to allow the production to take place in areas connected in a logical order corresponding to the sequence of the operations and to the requisite cleanliness levels • Working and in-process storage space should be adequate to permit orderly and logical positioning of equipment and materials to minimize risk of confusion between different pharmaceutical products or their components, to avoid cross-contamination and to minimize the risk of omission or wrong application of any of the manufacturing or control steps • The premise must have good pipe work, light fittings and ventilation points (air handling system) • Design of the premise must include the following design features; o Design of facilities required ▪ Adequate space for future expansion ▪ Zoning laws –to allow anticipated development, restricting undesirable developments in the vicinity ▪ Availability of water (quality and quantity), power, fuel, sewage and waste removal ▪ Accessibility to employees, materials and visitors ▪ Environmental issues such as site history (soil, water, and air quality) ▪ Proximity of undesirable activities likely to cause pollution ▪ Availability of a suitable labour force ▪ Ability to provide adequate security arrangements ▪ Political situation ▪ Government stability, trade policies and taxation, financial incentives o Design of Ancillary areas ▪ Rest and refreshment rooms must be separated from manufacturing and control areas ▪ Facilities for changing and storing clothes and for washing appropriate to the number of workers ▪ Toilets should not communicate directly with production or storage areas ▪ Maintenance workshops (should be separated from production area) ▪ Animal houses should be well isolated from other areas with separate entrance (animal access) and air handling facilities o Design of Storage areas ▪ Storage areas should have sufficient capacity for orderly storage of various categories of materials and product with proper separation and segregation ▪ Storage areas should be designed or adapted to ensure good storage conditions ▪ Special storage conditions (provided, controlled, monitored and recorded appropriately) ▪ Quarantine area must be allocated to restrict access to unauthorized personnel ▪ Secure areas for storage of controlled

NTA Level 6 • Semester 1 • PST06103 In-process Quality Control (IPQC) Pharmaceutical Production • Source Session/Topic 22 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 22: In-process Quality Control (IPQC) 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 concept of in-process quality control • List tests and equipment/apparatus used for in-process quality control of tablets and capsules • Explain the consequences of in-process quality control of tablets and capsules • List the objectives of in-process quality control 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 |Buzzing |The Concept of In-process Quality | | | |Presentation |Control | |3 |20 Minutes |Presentation |Objectives of In-process Quality | | | | |Control | |4 |55 Minutes |Presentation |In-process Quality Control Tests in | | | | |the Manufacture of Tablets and | | | | |Capsules | |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: The Concept of In-process Quality Control (25 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |What is in-process quality control? | | | |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 | • In-process quality control is a type of quality control that provides accurate specific and definite description of procedure to be employed from the receipt of raw material to the release of the finished product • In-process quality control performs checks during production in order to monitor and, if necessary, to adjust the process to ensure that the product conforms to its specifications • In-process quality controls are usually performed within the production area. The performance of such in-process controls should not have any negative effect on the quality of the product or another product • Generally, the in-process control procedures are usually rapid and simple tests or inspections that are performed when the manufacturing of a product batch is in progress STEP 3: Objectives of In-process Quality Control (20 minutes) • Some of the objectives of in-process quality control are; o To minimize human errors o To provide accurate, specific and definite description of the procedure to be employed in manufacturing of a product o To detect errors if and when they occur o To pin point responsibility to the personnel involved in the operation of the entire process o To ensure that the flow of manufacturing and packing operations according to established routes and practice is rigidly followed o To detect abnormality immediately and at the same time indicate action needed to correct the problem STEP 4: In-process Quality Control Tests in the Manufacture of Tablets and Capsules (55 minutes) • Evaluation of dosage forms (tablets); o General appearance ▪ Size, shape and texture ▪ Unique identification markings (embossing, engraving or printing) ▪ Organoleptic properties (e.g. colour distribution, taste, odour) o Content uniformity test ▪ 30 tablets are kept aside (sampled), 10 tablets are assayed, 9 tablets should have percentage limit of 85-115% ▪ If more than 1 tablet has 85-115%, then, 20 tablets are assayed and not more than 1 tablet should have 75-125% o Tablet hardness test or tablet crushing strength ▪ Hardness of a tablet is the force required to break a tablet in a diametric compression test ▪ Hardness testing is a laboratory technique used to test the breaking point and structural integrity of tablet under conditions of storage, transportation, and handling before usage (breaking point of a tablet is based on its shape) ▪ Tablet hardness is tested by using Tablet Hardness Tester e.g. Monstanto hardness tester, Stokes harness tester, Erweka tester, Schleuniger or heberlein tester, Strong Cobb tester and Pfizer hardness tester ▪ Conventional tablet hardness: 2.5 – 5 kg/cm2 ▪ Dispersible/chewable tablet hardness: 2.25 -2.5 kg/cm2 ▪ Extended release tablets hardness: 5-7.5 kg/cm2 o Friability ▪ Friability is the tendency of tablets to powder chip or fragment. This affects the elegant appearance of tablets and consumer acceptance of the tablets ▪ Friability leads to variation in the weight and content of tablets ▪ Friability is related to hardness of a tablet ▪ Instrument used for friability testing is known as Friabilator (e.g. Roche friabilator) ▪ Consisting of a plastic chamber that revolves at 25 rpm dropping the tablets through a distance of 6 inches in the friabilator, which is then operated for 100 revolutions ▪ From the friabilator, the tablets are reweighed ▪ Loss in weight is determined ▪ Allowable range is 0.5 – 1.0% o Weight variation ▪ 20 tablets are taken (sampled) and weighed individually ▪ Average weight of the 20 tablets is determined ▪ Weight of individual tablet is compared to the average weight ▪ Not more than 2 of the individual tablet weights deviate from the average weight by more than the prescribed percentage deviation and none deviates by more than twice that percentage (e.g. USP limits, I. P limits) o Disintegration test ▪ For most tablets, the first important step towards formation of solution is break down of the tablet into smaller particles or granules i.e. disintegration ▪ Disintegration test is performed by use of the disintegration apparatus ▪ The disintegration apparatus is comprised of glasses and a

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,

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 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 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 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 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