PST Level 6 Semester 1

NTA Level 6 • Semester 1 • PST06103 Introduction to Pharmaceutical Production Pharmaceutical Production • Source Session/Topic 1 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 1: Introduction to Pharmaceutical Production Total Session Time: 60 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define terminologies used in pharmaceutical production • List the general requirements for pharmaceutical production • Outline products manufactured in Pharmaceutical Productions 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 |Definitions | | | |Presentation | | |3 |10 minutes |Presentation |Requirements for Pharmaceutical | | | | |Production | |4 |10 minutes |Buzzing |Products in Pharmaceutical | | | |Presentation |Productions | |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: Definitions (25 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |Define Good Manufacturing Practices | | | |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 | • Pharmaceutical production (pharmaceutical manufacturing) o This is the process of industrial (large) scale synthesis of pharmaceutical drugs by pharmaceutical companies • Batch, batch size an batch number o A batch is a quantity or consignment of pharmaceutical products produced in a single manufacturing run o The total number of items in one batch is the batch size o Each batch is given a specific identification code called the batch number • Batch production o This is a technique used in manufacturing, in which the object in question is created stage by stage over a series of workstations, and different batches of products are made • Batch Manufacturing Record (BMR) o A batch manufacturing record is a document designed to provide a complete record of the manufacturing history of a batch of product o BMR is also known as; ▪ BPR-Batch processing record ▪ BPCR-Batch processing and control record • Master Formula Record o A document or set of documents specifying the starting materials with their quantities and the packaging materials, together with a description of the procedures and precautions required to produce a specified quantity of the product as well as the processing instructions including the in-process controls o There are must be a master formula record for each product and batch size to be manufactured • Mixing is a process whereby different ingredients are put together to form a mixture • Weighing and Measuring o Weighing is a process of determining weight of ingredients (for example by using a weighing balance) o Measuring is the determination of volume of liquid ingredients by using graduated measures such as measuring cylinders, pipettes etc. • Tableting o This is a process of compressing powders or granules to form tablets • Tablet Press o This is an equipment that is used for manufacturing of tablets • Encapsulation o This is a process of enclosing powders, tablets, pellets, granules or liquids in shells commonly made up of gelatin to form capsules • Quality Assurance (QA) o It is a wide ranging concept covering all matters that individually or collectively influence the quality of a product • Good Manufacturing Practices (GMP) o GMP is a part of quality assurance (which sets out principles and procedures) that ensures that products are consistently manufactured and controlled to the quality standards appropriate to their intended use • Quality Control (QC) o It is part of GMP concerned with sampling, specifications and testing and with the organization, documentation and release procedures which ensure that the necessary the necessary and relevant tests are carried out and the materials are neither released for use nor products are used for sale or supply until their quality has been satisfactory • Active Pharmaceutical Ingredient (API) “Drug substance” o An ingredient which gives a drug its chief therapeutic value; i.e. responsible for pharmacological action. OR o Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when used in production of a drug, becomes an active ingredient of that drug. • Drug o Any chemical compound used on or administered to humans or animals as an aid in the diagnosis, treatment or prevention of disease or other abnormal condition, for the relief of pain or suffering, or to control or improve any physiologic or pathologic state. OR o Medicine, pharmaceutical substance which when absorbed into a living organism may modify one or more of its functions. • Drug Product o A unique combination of drug(s), strength and dosage form in which a drug is administered. • Finished Pharmaceutical Product o A medicinal product/dosage form which has undergone all stages of manufacture or production, including packaging in its final container and labeling. • Pharmaceutical Dosage form: o Is the form in which drugs are formulated and ready for delivery to the patients. E.g. solution, mixture, emulsion, suspension, injectable, tablets, capsules etc • Excipients or Additives or adjutants. o A chemical substance/additive with no pharmacological action, used in the formulation of dosage forms. Vehicle for the drug. o A substance, other than the active ingredient, which has been appropriately evaluated for safety and is included in a drug delivery system to: ▪ aid in the processing of the drug

NTA Level 6 • Semester 1 • PST06103 Registration and Regulation of Pharmaceutical Manufacturing in Tanzania Pharmaceutical Production • Source Session/Topic 2 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 2: Registration and Regulation of Pharmaceutical Manufacturing in Tanzania 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 registration of businesses in Tanzania • Explain the role of Tanzania investment centre in promoting pharmaceutical manufacturing • Outline the licensing of businesses in Tanzania • Explain the role of TFDA in establishing and regulating manufacturing of pharmaceuticals • Explain the role of TRA pharmaceutical 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 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |25 minutes |Buzzing |Company Registration | | | |Presentation | | |3 |20 minutes |Presentation |Investment Approval | |4 |20 Minutes |Presentation |Business Licensing | |5 | |Small group |Medicine Manufacturing Licence | | |30 Minutes |discussion | | | | |Presentation | | |6 |10 minutes |Presentation |Taxes in Pharmaceutical Manufacturing| |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: Company Registration (25 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |How are companies or businesses registered in Tanzania? | | | |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 order to do business in Tanzania, a business entity in form of a sole proprietorship, partnership or limited liability company needs to be formed • The business entity in form of sole proprietorship, partnership must be registered with the Business Registration and Licensing Agency (BRELA) which is under the Ministry of Industries and Trade • The first step in registration of the business name is to obtain name clearance from BRELA • Generally, the following documents are required for in the process of forming a company; o Name of the company o The address of the company in Tanzania o Names, residential addresses and nationalities of the first subscribers and directors (at least two) o Memorandum of Association (stating in details the objects of the company) and Articles of Association (stating in details the management structure and processes) ▪ At least two copies of the documents each documents are required o Filling a prescribed form to declare that a company has complied with the requirements of the Tanzania company law, and o Payment of filing fees, registration fee and the stamp duty • A certificate of registration (for sole proprietorship and partnership) or Incorporation (for a limited company) is issued after completion of the registration process • After registering the name of the company, Tax Identification Number (TIN) should be obtained from Tanzania Revenue Authority (TRA) STEP 3: Investment Approval (20 minutes) • In order to make investment incentives from Tanzania Investment Centre (TIC), the following documents are required; o Project’s business plan/feasibility study ▪ Intended project should aim at foreign exchange generation and savings, import substitution, creation of employment opportunities, linkage benefits, transfer of technology, expansion of production of goods and services etc. ▪ The feasibility study should contain clear statement of the project objective, information regarding the investor, details of investments costs (foreign and local expected capital expenditure), how the proposed investment will be financed, specific sources(s) of finance for the project, terms and condition of loans if applicable, sources of technology if applicable, project financial and economic analysis, market study, project capacity, production process if applicable, environmental impact assessment, expected employment generation, proposed implementation schedule, etc. o Filled application form from issued by TIC o In case of expansion/rehabilitation, a copy of audited account for the past three years o A copy of the company’s Memorandum and Articles of Association o Certified copy of the Certificate of company incorporation o A brief profile of the investor(s) o Evidence of sufficient financial capital available to implement the project o Evidence of land ownership for the location of the project o Project implementation schedule, and o An overall covering letter to which all the above are attached • The role of TIC in promoting investment in pharmaceutical industry are; o Aftercare service ▪ This is a core functional unit in investment promotion and facilitation whose role to facilitate both the successful start-up and continuing development of the investment with a view towards maximizing its contribution to the local economic development ▪ Aftercare unit offers assistance in ensuring that the investment project is implemented free of unnecessary obstacles o Access to various services related to permits, licenses and approvals in the TIC One Stop Facilitation Centre ▪ Companies Registration (BRELA) for registration of company ▪ Tanzania Revenue Authority (TRA) for issues related to taxes ▪ National Environment Council (NEMC) for environmental impact assessment ▪ Tanzania Foods and Drugs Authority for licensing in manufacturing of pharmaceutical products ▪ Tanzania Electric Supply Company (TANESCO) for electric power supply ▪ IOccupational Health and Safety Authority (OSHA) for issues related to occupational health ▪ Facilitates the process of obtaining work permit, resident permit, business license and land acquisition o Issuance of Certificate of incentives to investors ▪ Incentives offered; ▪ The recognition of private property and protection against any non-commercial risks. Tanzania is an active member of the World Bank

NTA Level 6 • Semester 1 • PST06103 Environmental Impact Assessment (EIA) Pharmaceutical Production • Source Session/Topic 3 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 3: Environmental Impact Assessment (EIA) Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Describe environmental management in Tanzania • Define environmental impact assessment • List key features and elements of environment impact assessment • Explain the importance of environmental impact assessment • List stakeholders of environmental impact assessment • Outline the steps in conducting environmental impact assessment Resources Needed • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer • Handout 3.1: Steps to Conduct Environmental Impact Assessment SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |15 minutes |Presentation |Environment management in Tanzania | |3 |15 minutes |Presentation |Environmental Impact Assessment | |4 |20 minutes |Presentation |Features and Key Elements of an | | | | |Effective EIA | |5 |10 minutes |Brainstorming |Stakeholders in EIA | | | |Presentation | | |6 |10 minutes |Buzzing |Importance of EIA | | | |Presentation | | |7 |35 Minutes |Presentation |Steps to Conduct EIA | |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: Environment Management in Tanzania (15 minutes) • Management of environment in Tanzania is carried out by the National Environment Management Council (NEMC) which came into being in 1983 when the Government of Tanzania enacted the National Environment Management Act No. 19 of 1983 • NEMC was established with a broad mandate in response to the national need for such an institution to oversee environmental management issues and also implement the resolutions of the Stockholm conference (1972), which called upon all nations to establish and strengthen national environmental Councils to advise governments and the international community on environmental issues • The Environmental Management (EMA) Act No. 20 of 2004 provides for a legal and institutional framework for sustainable management of the environment, prevention and control pollution, waste management, environmental quality standards, public participation, environmental compliance and enforcement • EMA also gives NEMC mandates to undertake enforcement, compliance , review and monitoring of environmental impacts assessments, research, facilitate public participation in environmental decision-making, raise environmental awareness and collect and disseminate environmental information • Some of the objectives of NEMC are; o To enforce and ensure compliance of the national environmental quality standards. o To review of Environmental Impact Statements (EIS) and conduct environmental monitoring and auditing of projects and facilities o To undertake and co-ordinate research, investigation and surveys in the field of environment and collect, and disseminate information o To carry-out research and surveys for the proper management and conservation of environment o To render advise and technical support to entities engaged in natural resources and environmental management o To initiate and evolve procedures and safeguards for the prevention of accidents which may cause environmental degradation o To enhance environmental education and public awareness; and establish and operate national environmental information system for sound environmental management o To publish and disseminate manuals, codes and guidelines relating to environmental management and prevention or abatement of environmental degradation o To issue restoration and recommend for easements orders, and save prohibition notice STEP 3: Environment Impact Assessment –EIA (15 minutes) • Environmental Impact Assessment (EIA) is a process of evaluating the likely environmental impacts of a proposed project or development, taking into account inter-related socio-economic, cultural and human-health impacts, both beneficial and adverse • EIA is a national instrument that is undertaken for proposed activities that are likely to have a significant adverse impact on the environment and are subject to a decision of a competent national authority • EIA is used to improve decision-making and ensure that development options under consideration are environmentally, socially and economically sound and sustainable • EIA is concerned with identifying, predicting and evaluating the foreseeable impacts, both beneficial and adverse, of proposed development projects and alternatives • EIA aims to eliminate or minimise negative impacts and optimise positive impacts through mitigation and enhancement measures • EIA relates to a process rather than a particular activity, t 0he environmental impact study itself being only one component of the process STEP 4: Features and Key Elements of an Effective EIA (20 minutes) • EIA is a continuous and integral component of planning that should run continuously throughout the planning cycle of any development initiative • EIA facilitates dialogue, prediction and response and provides a forum for proponents, decision-makers and the public, to consider the potential impacts of a project on local communities, natural resources and environmental quality • EIA helps to enhance social and economic opportunities, and to promote conservation and provides a mechanism for enhancing new economic and social opportunities and for introducing long-term environmental protection and conservation measures into project design • EIA provides a framework for stakeholder participation in decision- making, experience has shown that development projects imposed on local communities often fail to address issues of local concern and priority, and hence fail to engender a perception of local ownership • EIA is a tool to improve decision-making, and provides project-specific and strategic information before project implementation decisions are reached o It is also a mechanism for addressing cross-sectoral and cross- boundary issues o EIA helps to avoid inadvertent( Unplanned) problems and their associated costs during project design • The key elements of effective EIA system o A legal basis with accompanying regulations o Appropriate institutional arrangements for co-ordination and regulation of EIA system, e.g. by an environment agency

NTA Level 6 • Semester 1 • PST06103 Standard Operating Procedure (SOP) Pharmaceutical Production • Source Session/Topic 4 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 4: Standard Operating Procedure (SOP) Total Session Time: 120 minutes + 240 minutes of Assignment Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define standard operating procedure (SOP) • Explain the importance of SOP • Outline types of SOPs • Explain the components of SOP • Explain the development and approval processes of SOP Resources Needed • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer • Handout 4.1: Sample format for Writing SOP • Handout 4.2: Sample Guide for Writing Procedure Part of SOP SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |20 minutes |Presentation |Definitions | |3 |10 minutes |Presentation |Importance of SOPs | |4 |15 Minutes |Presentation |Characteristics of SOPs | |5 |35 Minutes |Presentation |General Formats for SOPs | |6 | |Small group |Writing SOPs | | |20 minutes |discussion | | | | |Presentation | | |7 |05 minutes |Presentation |Key Points | |8 |05 minutes |Presentation |Evaluation | |9 |05 minutes |Presentation |Development of SOP | | | |Take home | | | | |assignment | | 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 Standard Operating Procedure (SOP) (20 minutes) • Standard Operating Procedure (SOP) is a set of written instructions that document a routine or repetitive activity which is followed by employees in an organization • It is a set of compulsory instructions, systems, procedures or steps which is written so that other individuals can follow to complete the job safely and ensure quality • SOP maximizes operational and production requirements • The purpose of a SOP is to carry out the operations correctly and always in the same manner • SOP should be available at the place where the work is performed (original copies are securely kept) • There are two main types of SOPs o Technical SOP ▪ This focuses more on technical activities such as how to weigh pharmaceutical powders on dispensing balance or how to clean a tablet press o Administrative SOP ▪ This type focuses on administrative processes such as reviewing contract documentation and determining organizational training needs STEP 3: Importances of SOPs (10 minutes) • Standard Operating Procedures are integral part of all pharmaceutical industries • To obtain a standard quality product intended for human use, the manufactured product must have undergone through current Good Manufacturing Practices (cGMP) rules and regulations • SOPs are part of cGMP and Good Documentation Practices (GDP) • An SOP guides any process, procedure or activity being performed in the pharmaceutical plant • SOPs minimizes variation and promotes quality through consistent of a process or procedure even in cases of personnel changes • SOP can be used as part of personnel on-job training as it offers instruction on how to a job • SOPs minimizes opportunities for miscommunication and can address safety concerns • A typical pharmaceutical industry has an average of 1200 to 1300 SOPs o The guide on writing all these SOPs are provided by the Mother SOP (the SOP on SOPs) STEP 4: Characteristics of SOPs (15 minutes) • SOPs have a format and length that depends on the steps that are taken to describe the procedure of the work o An SOP can be a simple one page hierarchical steps, graphic procedures or a flow chart • SOP can be written by individuals or team performing processes such as operating a tumbler mixer or cleaning of an equipment • SOPs are written by subject expert considering the GMP working feasibility, accountability and authorized by authorized persons • The SOP is meant for people who will perform a particular job • The SOP should be written before the job is began • SOP should be tested (and revised as needed) before putting it into final application • SOP should be revised when there is any change to the process or equipment used • SOP should be re-written when new information indicate new process or performance • SOP should be updated regularly depending on internal and external factors STEP 5: General Format of SOPs (35 minutes) • Various formats exist for preparation of SOP • All Standard Operating Procedures shall be written in a certain format specified in the mother SOP (SOP on SOPs) • Choice of a format depends on the organization and type of activity for which the SOP is prepared • Generally, a technical SOP consists of the following components o Title Page ▪ This is the first page or cover page of the SOP ▪ This part contains the following information ▪ Title (which clearly identifies the activity or procedure) ▪ SOP identification number ▪ Supersedes (number of previous SOP on which the current one is based or reviews) ▪ Date of issue and/or revision ▪ Name of the organization or company ▪ Department to which the SOP applies ▪ Signatures of individuals who prepared the SOP ▪ Signatures of individuals who approved the SOP o Table of Contents ▪ Needed for quick reference, especially if the SOP is long ▪ It is also needed for locating information and to denote changes or revision made only in certain sections of an SOP o Purpose/Objective ▪ This describes the purpose of the work or process including any regulatory information or standards that are appropriate to the SOP o Scope ▪ This indicates what is covered e.g. this procedure is applicable to all operation of this company (company

NTA Level 6 • Semester 1 • PST06103 SOP on SOPs (SOP on Standard Operating Procedures) Pharmaceutical Production • Source Session/Topic 5 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 5: SOP on SOPs (SOP on Standard Operating Procedures) Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define SOP of SOPs • Explain the components of SOP of SOPs • Develop an SOP of SOPs Resources Needed: • Flip charts, marker pens, and masking tape • Black/white board and chalk/whiteboard markers • LCD projector and computer • Handout 5.1: Format for SOP of SOPs SESSION OVERVIEW |Step |Time |Activity/ |Content | | | |Method | | |1 |05 minutes |Presentation |Introduction, Learning Tasks | |2 |05 minutes |Presentation |Definition | |3 |10 minutes |Presentation |Components of SOP of SOPs | |4 | |Small group |Development of SOP of SOPs | | |90 Minutes |activity | | | | |Presentation | | |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: SOP of SOPs (5 minutes) • In order to write Standard Operating Procedure, another Standard Operating Procedure is needed to standardize and guide the process • The SOP that guides how other SOPs in the organization should be prepared is known as an SOP of SOPs or a mother SOP STEP 3: Components of SOP of SOPs (10 minutes) • Components of the SOP of SOPs; o Purpose ▪ The purpose of SOP of SOPs is to describe procedures for preparation, review and approval of standard operating procedures in pharmaceutical production o Scope ▪ This part of the SOP of SOPs describes the way the SOP of SOPs applies to all SOPs o Responsibility ▪ This part identifies people (Executive/QA officers or other designated persons) responsible for preparation, revision, periodical review and approval of the SOP of SOPs ▪ Persons responsible for the preparation, revision and periodic review of the SOP of SOPS ▪ Person(s) responsible for review and training of the SOP of SOPs ▪ Person(s) responsible for approval of the mother SOP o Procedure ▪ This part should, ▪ Specify the format of all SOPs in the organization ▪ Specify paging and placement of company logo on SOPs ▪ Specify header, content and footer of the SOPs ▪ Specify font style, font size and line spacing in all SOPs ▪ Specify numbering system (and description of characters used in the numbering system) for the SOPs ▪ Specify placement of dates (supersedes, approval date, effective date and review date) for SOPs ▪ Specify the signatories of various SOPs in the organization (i.e. prepared by, reviewed by, approved by) ▪ Specify the content of SOPs ▪ Purpose, scope, responsibility, procedure, revision, abbreviations, annexures, header, footer, as described in session 7) o Revision ▪ Describes revision of SOPs ▪ Provides a revision log showing revision number, effective date and reason for the revision of each SOP revised o Abbreviations ▪ Should show abbreviations or acronyms used in the mother SOP and their expanded form o Annexure ▪ Provides a list of all the annexure used in the mother SOP (e.g. SOPs format, list of codes) STEP 5: Developing an SOP of SOPs (90 minutes) [pic][pic] Refer students to Handout 5.1: Format for SOP of SOPs |Activity: Small Group Assignment (60 minutes) | | | |DIVIDE students in manageable groups | | | |ASK the students to work on the following assignment | | | |Prepare an SOP of SOPs for a Compounding Laboratory in your school | | | |ALLOCATE time for students to do the assignment and presentation | | | |REFER students to recommended references | STEP 6: Key Points (5 minutes) • SOP on SOPs is the standard operating procedure for preparation of all SOPs in an organization • It guides the process of preparing SOPs in all departments of an organization • SOP of SOPs is also known as the mother SOP STEP 7: Evaluation (5 minutes) • What is an SOP? • What is SOP of SOPs? • Mention the components of an SOP of SOPs • Who is responsible for preparing the SOP of SOPs in a pharmaceutical manufacturing company? References Escope, Adriene, (1997). Nimble documentation, the practical guide for World class organization, Milwaukee, Wisconsin, American Society for Quality, Quality Press Garner, Willa Y and Mureen S. Barge, Editors, “Good Laboratory Practices. An agrochemical perspective” ACS Symposium Series 369, American Chemical Society Schmidt, O. (ed) (2000) Pharmaceutical Quality systems, Interpharm Press, Colorado. Shayne C et al (2008), Pharmaceutical Manufacturing Handbook: Production and processes, John Wiley & Sons |[pic] |Handout 5.1: General Format for SOP of SOPs | | SOP ON STANDARD OPERATING PROCEDURES | |Title: |Copy no.: | |Organization/Company: |Page no.: | |SOP of SOPs No.: |Supersedes: | | |Effective date: | |Review Date: |Prepared By |Reviewed By |Approved By | |Designation | | | | |Signature and Date | | | | 8. Purpose 9. Scope 10. Responsibility 11. Procedure 12. Revision 13. Abbreviations 14. Annexures ← Previous TopicNext Topic →View all Pharmaceutical Production topicsOpen Complete Full Notes PDF / OFFLINE NOTES Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP WhatsApp: 255620339260

NTA Level 6 • Semester 1 • PST06103 Validation of Pharmaceutical Raw Materials Pharmaceutical Production • Source Session/Topic 6 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 6: Validation of Pharmaceutical Raw Materials 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 raw materials • Explain the validation process for pharmaceutical raw materials • Explain the approaches and importance of raw materials testing • List tests and equipments used for testing quality of raw materials 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 |Presentation |Definition of raw materials | |3 |40 minutes |Presentation |Validation of Pharmaceutical Raw | | | | |Materials | |4 |20 minutes |Presentation |Approaches and Importance of Raw | | | | |Materials Testing | |5 |30 Minutes |Presentation |Tests and Equipments for Raw | | | | |Materials Validation | |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: Definition of Raw Materials (15 minutes) • Pharmaceutical raw materials are the starting materials in the manufacturing of a finished pharmaceutical product • Raw materials are used in the manufacturing of a finished bulk (even though it may not be present in the final product e.g. certain solvents etc.) and are consumed by person using the product • Pharmaceutical raw materials include the active drug and the inactive substances (the excipients) STEP 3: Validation of Pharmaceutical Raw Materials (40 minutes) • Pharmaceutical raw materials must be validated for quality attributes (identity, safety, potency, purity, stability and efficacy) • Validation of pharmaceutical raw materials o It is a process of demonstrating through documented evidence that the raw materials will consistently produce a product or result that meets predetermined specifications and quality attributes in the final product • Steps required in validation of raw materials are; o Preparing a list of all raw materials needed to prepare a product batch ▪ Should include all materials used in production and testing including active ingredients and excipients o Identification of suppliers for each raw materials ▪ Purchase specifications for raw materials for pharmaceutical manufacturing should be established and used in order to ensure acquisition of quality raw materials and hence quality finished products ▪ Mode of purchasing should be specified e.g. by inspection, by sample, by description brand or by grading ▪ Visiting the suppliers’ warehouse to inspect storage of raw materials (how quality is maintained) especially for a new supplier o Obtaining samples and supplier’s certificates of analysis ▪ To determine characteristics of raw materials ▪ Certificates of analysis and samples show the extent of variation between different lots from the same supplier and the variation between suppliers o Establishing specifications for each raw material ▪ The list of parameters show acceptable measurable range of activity for compendial raw materials and non compendial raw materials o Establishing optimum storage conditions ▪ Raw materials must handled and stored under prescribed condition in order to protect their stability over stated shelf-life • Primary objective in storage of raw materials once accepted is to protect their quality and prevent loss through spoilage or theft • External containers must be cleaned before storage • Quantity must be verified • Storage as per quarantine status of the materials o Received, sampled, approved, rejected o Space should be defined for each item or type of item ▪ Chemistry of each raw material should be reviewed and aspects concerning hygroscopic nature, photosensitivity, sensitivity to temperatures, ability to support microbial growth, reactivity with container or closure system and oxidizing capacity are checked o Establishing sampling procedures ▪ Visual inspection on receipt of the raw materials (based on detection of physical damage to package, lids or seals; proper labelling)may not enough to ascertain quality of raw materials ▪ Raw materials must be sampled for laboratory testing ▪ In order to conduct test for raw materials, documentation of raw material sampling (SOP) must be developed ▪ Documentation of sampling include general requirements for any raw materials received in the plant; ▪ Quantity of raw material received and number of containers to sample (sample size) ▪ Sampling responsibility (who should collect the samples) ▪ Sampling formula used ▪ Method of sampling e.g. top, middle, bottom • Individual raw materials may have their own sampling requirements based on their stability and/or intended use o Establishing test procedures for raw materials ▪ Before manufacturing begins, all raw materials must be tested (for safety, purity, identity and quality) ▪ A test procedure must be established for each specification ▪ For raw materials that are compendia, test procedures are denoted along with their respective specifications ▪ For raw materials that are not listed in official compendia, methods are developed for their testing (through modification of compendia methods that exist for similar compounds or methods published in literature) ▪ Extent of raw material testing is determined by the manufacturer STEP 4: Approaches and Importance of Raw Materials Testing (20 minutes) • Before finished pharmaceutical dosage forms are produced, the identity, purity and quality of raw materials must be established with the use of suitable test methods • Several approaches are used by manufacturers to raw materials testing in order to comply with national and international standards and regulations o One such approach by manufacturing company is performing an initial detailed vendor audit followed by an annual qualification consisting of full pharmacopoeial monograph testing on three lots of materials. If the qualification lots

NTA Level 6 • Semester 1 • PST06103 Dispensing of Pharmaceutical Materials Pharmaceutical Production • Source Session/Topic 7 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 7: Dispensing of Pharmaceutical Materials Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Dispensing of raw materials • Describe dispensing area for raw materials • List equipment used in dispensing of raw materials • Explain the dispensing of raw materials 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 |Dispensing and Dispensing Area | |3 |20 minutes |Buzzing |Dispensing Equipments | | | |Presentation | | |4 |25 minutes |Presentation |Preparation for Dispensing Raw | | | | |Materials | |5 | |Small group |Dispensing Process for Pharmaceutical| | |40 minutes |discussion |Raw 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: Dispensing and Dispensing Area (20 minutes) • Dispensing of raw materials is the process whereby raw materials required for production are identified, weighed or measured and transferred to the production area • Every pharmaceutical manufacturing plant must have an area in which raw materials are weighed and transferred in clean containers to the production area • The area where dispensing takes place is known by various names including weighing bay, weighing area, weighing room, central weigh, pharmacy or dispensing room • Features of a weighing room include; o Unidirectional flow of materials and personnel o Segregation between hazardous and non-hazardous materials o Separation of storage and manufacturing items and space • The weighing room is the entry point to manufacturing and the transition point for materials coming from the warehouse and entering processing areas • The dispensing areas is commonly comprised of; o Weighing area ▪ Where actual weighing or measuring of raw materials is done o Raw material staging area ▪ When weighing is complete, there may still be material left in the containers received from the client ▪ Large quantities are usually returned to the warehouse, but small quantities, especially of those materials that will be used again soon, can be stored on pallets or on shelving in raw material staging areas (materials requiring special storage conditions not provided by the raw material staging area are returned to their appropriate storage locations in the warehouse) o Work-in-process STEP 3: Dispensing Equipments (20 minutes) |Activity: Buzzing (5 minutes) | | | |ASK students to pair up and buzz on the following question for 2 | |minutes | | | |Which equipments are used in dispensing of raw materials? | | | |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 | • Dispensing equipment include the following; o Scales ▪ Size of scale used is determined by capacity of materials to be weighed ▪ Example is a pit-mounted floor scale o Pippetes o Calibrated measuring containers o Fume cabinets o Labels/printers and related instrumentation • All equipment must be calibrated and maintained regularly to minimize errors o Routine testing must be carried out for all the balances being used in the facility • All dispensing equipment must be documented properly • There should be SOP for using each equipment STEP 4: Preparation for Dispensing Raw Materials (25 minutes) • Before any dispensing activity is done, the warehouse, in-process quality control and production personnel must ensure that ; o The dispensing area and dispensing equipment are cleaned o Differential pressure, temperature and relative humidity of the dispensing area are within the specified limits o Documents related to previous products are removed from dispensing area o All the log books of the respective areas are updated o Approved materials are to be dispensed o The reverse laminar flow (RLAF) is switched on 15 minutes before dispensing activity starts • Production personnel is responsible for calculating the quantity of active pharmaceutical ingredients (APIs) and excipients (and adjustments according to standard batch size, if applicable) as outlined in the Batch Manufacturing Record (BMR) o The calculations are verified by in-process quality control personnel • Personnel enter the dispensing area through the personnel airlock with proper gowning • Dispensing is only done in controlled conditions under reverse laminar air flow STEP 5: Dispensing Process for Pharmaceutical Raw Materials (40 minutes) |Activity: Small Group Discussion (10 minutes) | | | |DIVIDE students into small manageable groups | | | |ASK students to discuss on the following question | |Explain the dispensing procedures for raw materials? | | | |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 | o Receipt of “Dispensing of Raw Material Sheet” ▪ The Batch Manufacturing Record (BMR) contains a list of raw materials to be dispensed known as Dispensing of Raw Material sheet ▪ All raw materials are dispensed as per quantities mentioned in the “dispensing of raw material” sheet of the BMR o Verification of Availability ▪ Warehouse personnel verifies the availability of the approval status of required raw materials ▪ A raw materials stock card of respective raw material is used to facilitate the verification process o Dispensing the raw material ▪ After verification of availability, warehouse

NTA Level 6 • Semester 1 • PST06103 Pharmaceutical Powders Pharmaceutical Production • Source Session/Topic 8 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 8: Pharmaceutical Powders Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define powders • Explain the production of powders • Classify powders • List uses of powders in pharmacy • List advantages and disadvantages of powders 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|Brainstormin| Introduction to Powders | | | |g | | | | |Presentation| | |3 |10 minutes|Presentation|Production of Powders | |4 |30 minutes|Presentation|Preparation and Mixing of Powders | |5 |30 minutes|Presentation|Bulk and Divided Powders | |6 | |Small group |Advantages and Disadvantages of | | |20 minutes|discussion |Powders | | | |Presentation| | |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: Introduction to Powders (15 minutes) |Activity: Brainstorming (5 minutes) | | | |ASK students to brainstorm on the following question: | | | |What is a pharmaceutical powder? | | | |ALLOW few students to respond? | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY Al,0.++23.2+0000.nd SUMMARISE by using the content below | • A pharmaceutical powder is a mixture of finely divided drug and /or chemicals in dry form intended for internal or external use. • Powders are intended to be used as; o Dosage forms e.g. dusting powders o Starting materials for other dosage forms e.g. tablets and capsules ▪ They determine behavior of dosage forms during manufacturing and in the finished dosage form ▪ Particle size, density and porosity are important characteristic of powders • These affect the ability of powders to flow (flowability) ▪ Flowability may be measured by using the angle of repose • Powders as dosage forms can be classified according to; o Number of constituents ▪ Simple powders i.e. powders containing only one ingredient ▪ Compound powders i.e. powders containing two or more substances mixed together o Mode of application ▪ Powders for internal use ▪ Powders for external use o Packaging ▪ Bulk powders ▪ Divided powders STEP 3: Production of Powders (10 minutes) • Molecular aggregation o Precipitation ▪ Through super-saturation of solutions o Crystallization ▪ Through super cooling of solutions o Spray-drying ▪ Atomization of solution followed by evaporation of solvent • Particle size reduction o By use of equipment such as course crushers, grinders, and mills STEP 4: Preparation and Mixing of Powders (30 minutes) • Preparation of powder dosage forms o Preparation of powders involves o Particle size reduction (all ingredients) to the same range in order to prevent demixing or segregation ➢ Trituration (using mortar and pestle) ➢ Pulverization by intervention (for gummy or materials difficult to grind) ➢ Levigation o Sieving o Weighing of each ingredient o Mixing o Packaging • Mixing of Powders o Mixing is as an operation in which two or more components in a separate or roughly mixed condition are treated so that each particle lies as nearly as possible in contact with a particle of each of the other ingredients o For mixing to occur the individual particles must be redistributed repeatedly within the bulk, either by tumbling, shearing, scooping, kneading or impaction. o Powders are mixed to obtain homogeneity. Equipment used for mixing are known as mixers o For small scale mixing e.g. in compounding, equipments used for mixing are; ▪ mortar and pestle ▪ spatula and tile or paper ▪ sieving equipment (sieving) o For large scale mixing e.g. in industrial production, large mixers including ➢ tumbler mixers, ➢ shear mixers, ➢ ribbon mixers, ➢ impact mixers etc are employed ▪ Characteristics of an ideal mixer • Capable of producing complete blend in reasonable time without damaging the product • Dust-tight • Requiring low maintenance and energy • Discharged and cleaned easily (All these properties cannot be found in a single mixer) o Methods used in mixing powders ▪ Spatulation ▪ Trituration (for both comminution and mixing) ▪ Geometric dilution ▪ Sifting ▪ Tumbling • Types of powder mixtures o Free flowing mixtures o Cohesive mixtures o Ordered mixtures o Packaging of Powders ▪ Packed depending on use; ▪ Bulk powders ▪ Divided powders STEP 5: Bulk and Divided Powders (30 minutes) Bulk powders • Bulk powders are limited to non potent drugs • They are packed into suitable bulk containers to facilitate dosing (e.g. wide mouth jar, perforated or sifter top cans and aerosol containers) • Examples for powders commonly dispensed in a bulk form o Powders used in a dry form e.g. dusting powders, insufflations, dentifrices o Powders to be dissolved in water before use e.g. antacid powders, douche powders o Powders for reconstitution e.g. oral antibiotic powders, powders for injection (powders for injection may also be supplied as divided powders) • Bulk powders are classified into bulk powders for internal use and bulk powders for external use o Bulk Powders for Internal Use ▪ Contain several doses ▪ Dispensed in bulk ▪ Bulk powders for (oral) internal use are generally supplied as finely divided powders or effervescent granules • The finely divided powders are intended to be suspended or dissolved in water or mixed with soft foods, e.g., applesauce, prior to administration ▪ They include; antacid powders, oral antibiotic powders, laxative powders o Oral Powders ▪ These generally are supplied as finely divided powders or effervescent granules ▪ Granules are aggregates of powdered materials as

NTA Level 6 • Semester 1 • PST06103 Mixing of Pharmaceutical Powders Pharmaceutical Production • Source Session/Topic 9 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 9: Mixing of Pharmaceutical Powders Total Session Time: 120 minutes Pre-requisites • None Learning Tasks By the end of this session students are expected to be able to: • Define mixing • Explain the importance of mixing in pharmacy • Explain type of powder mixtures • Explain the mixing and de-mixing of powders • Explain mixing techniques • List types of mixers • Explain the selection and working of mixing equipments (mixers) 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|Presentation |Definitions | |3 |10 minutes|Brainstorming |Reasons for Mixing | | | |Presentation | | |4 |20 minutes|Presentation |Types of Powder Mixtures | |5 |30 minutes|Presentation |Mechanisms of Mixing and De-mixing of | | | | |Powders | |6 |30 minutes|Presentation |Mixing Techniques and Equipments | |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: Definition (15 minutes) • Majority of active ingredients and adjuvant (excipients) used for the manufacture of pharmaceutical dosage forms constitute in the powder form o Hence handling and processing of powders is central to pharmaceutical operations • Mixing and blending of bulk solids occurs frequently in pharmaceutical manufacturing • The term mixing and blending are often used interchangeably • Mixing o Mixing is defined as a process of thoroughly combining different materials to achieve a homogenous product ▪ In most cases the mixture is a combination of dissimilar material e.g. a drug and a diluents although at times, a chemically homogenous material is mixed to uniformly distribute its large range of particle sizes o Mixing of powder is a shuffling type unit operation process involving both large and small particle groups and even individual particles o Mixing is an energy consuming process which produces a random distribution of particles o Optimum mixing is a prerequisite for manufacturing of solid dosage forms which involve powder mixing and it has a critical contribution in achieving uniformity of content STEP 3: Reasons for Mixing (10 minutes) |Activity: Brainstorming (5 minutes) | | | |ASK students to brainstorm on the following question: | | | |What are the reasons for mixing powders? | | | |ALLOW few students to respond? | | | |WRITE their responses on the flip chart/ board | | | |CLARIFY and SUMMARISE by using the content below | • Mixing is done for the following reasons; o To ensure an even distribution of the active component(s) o To ensure an even appearance of the dosage form o To ensure that the dosage form releases the drug at the correct site and at the desired rate o To ensure colour uniformity since powders differs in colour STEP 4: Types of Powder Mixtures (20 minutes) • Free flowing mixtures o Free flowing powders have desirable features like minimal need of lubricant and effective contact with die cavity o They suffer from a serious drawback of segregation of individual components in post mixing processing o The particles can move smoothly and independently in a particular direction due to the inter-particulate forces o The free flowing powders need to be handled and stored in a proper manner by packing the products in polythene bags and applying vacuum, before sealing. • Cohesive mixtures o The cohesive mixture exhibits “stick-slip” characteristics and the components are not free flowing, the individual particles are repeatedly broken down and allowed to redistribute within the system to ensure a satisfactorily mixed product. The scale of segregation is less, but the intensity of segregation will be more due to the retaining of structure by the small agglomerates throughout the mixing process o Some of the parameters contributing to the formation of cohesive mixtures are moisture, electrostatic charges, Van der waals forces and solid bridges between the particles • Ordered mixtures o If one of the constituents of the powder mix is added to a fine, micronized form then on mixing the larger particles may adsorb some of these smaller particles to active sites on their surface where they are held tenaciously o Ordered mixtures are formed by mechanical, adhesion or coating forces such that the ordered unit will be the smallest possible sample of the mix and will be of near identical compositions to all other ordered units in the mix STEP 5: Mechanisms of Mixing and De-mixing of Powders (30 minutes) • Diffusion o Diffusion blending is characterised by the random motion of solid particles i.e. diffusive movement of individual particles (Micromixing) o It occurs where the particles are distributed over a freshly developed interface o It is a slow blending mechanism o This type of mixing is achieved by tumbler mixers • Convection o Mixing by convection is characterised by random motion of solid particles whereby blending groups of particles (a large portion of the powder bed) are rapidly moved from one position to another due to the action of a rotating agitator (Macromixing) o The movement of solid particles through the mixer is either by a force action from a paddle or by gentle tumbling under rotational effects o The blending of solids in ribbon blenders and paddle mixer is mainly a result of convective mixing • Shear o Shear mixing is achieved by the removal of force of attraction between the powder particles o Shear blending as the development of slip planes or shearing strains within a bed of material o Shear mixing

NTA Level 6 • Semester 1 • PST06103 Introduction to Capsules Pharmaceutical Production • Source Session/Topic 10 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 10: Introduction to 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 capsules • Classify capsules • Explain modified release capsules • List advantages and disadvantages of 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 |15 minutes |Presentation |Definitions | |3 |25 minutes |Presentation |Classification of Capsules | |4 |30 minutes |Presentation |Modified Release Capsules | |5 | |Small group |Advantages and Disadvantages of | | |35 minutes |discussion |Gelatin Capsules | | | |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: Definitions (15 minutes) • Capsules are solid unit dosage forms with hard or soft shells of various shapes and capacities containing a single dose of a drug substance • The term capsule is derived from the Latin word “capsula”, meaning a small container. • The first capsule prepared from gelatin was a one-piece capsule patented in France by Mothes and Du Blanc in 1834 • Capsules are intended to be swallowed whole; however, some soft gelatin capsules are intended for rectal or vaginal insertion as suppositories. • Capsules consists of two main parts, the shell (commonly but exclusively made up of gelatin) and the fill material (the Active pharmaceutical ingredient(s) and the excipients) o The capsule shell may also be made up of plant materials e.g. vegicaps • Capsules are a common form of dosage for oral administration of pharmaceutical and nutraceutical products • Branding and dosage information may be printed on the outer surface of the capsule • Medication or ingredients inside the capsule (the fill content) may be in form of solid, liquid or paste depending on the active pharmaceutical ingredient (API) or, in the case of nutraceutical, on the form of the main nutrient (e.g. liquid fish oil) STEP 3: Classification of Capsules (25 minutes) • Capsules are classified as either hard or soft, depending on the nature of the shell o Hard shell capsules ▪ Hard gelatine capsules consist of a hard gelatine capsule shell encasing solid fill material ▪ Hard gelatin capsules are also known as dry-filled capsules or two pieces capsules ▪ Hard gelatin capsules consist of two parts known as capsule body (longer part) and the capsule cap (the shorter part) ▪ The drug substance placed in the body and the caps are slided over it, hence enclosing the drug substance ▪ The caps and body pieces of the capsule shell are supplied unlocked to be filled with the appropriate drug or nutraceutical ingredients o Soft shell gelatine capsules ▪ Soft gelatin capsules, also called soft gels, are thicker than hard shell gelatin capsules ▪ They are softer and hence easier to swallow ▪ They are made up of one piece and hemetically sealed ▪ They are softer due to addition of plasticizers (glycerin or sorbitol) in the gelatin ▪ The shell is usually made up of gelatin like in the hard shell gelatin capsule but softer and contain more water (generally between 6% and 13% by weight) and preservatives ▪ Soft gels can be filled with liquid (solution, suspension etc), semi solid or rarely solid materials which can be dissolved or suspended in water to form a paste mixture ▪ In other case the capsule may simply be filled with granules or powder ▪ Instead of gelatine, seaweed extract and gluten free starch are used in making up the soft shell (providing animal free product, suitable for strict vegetarians) ▪ The shell can be clear or coloured and there is a wide range of shapes, sizes and colours available ▪ They are suitable for vegetarians or people who do not prefer animal products ▪ They have low shell odour STEP 4: Modified Release Capsules (30 minutes) • Both hard or soft gel capsules can be chemically modified to control the release of the active pharmaceutical ingredient (s) • Delivery of the active ingredient from the capsule shell is usually effected by disintegration of the shell and disintegration of the fill content upon opening of the shell • The release of the active pharmaceutical ingredient(s) may be modified by various methods including; o Coating the capsule shell with a material through which the drug diffuses o Coating the capsule shell with a slowly dissolving coat that slowly releases the drug over time o Employing a system utilizing a semipermeable membrane that blocks the drug from diffusing out through the membrane, but where the water on the exterior of the membrane can diffuse into the formulation, allowing the drug to be released through channels within the membrane o Designing the capsule shell to resist disintegration by the stomach acid until it reaches the intestinal fluid where at a higher pH it breaks down and releases the active ingredients i.e. enterically coated capsules STEP 5: Advantages and Disadvantages of Gelatin Capsules (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 advantages and disadvantages of capsule dosage forms? | | | |ALLOW students to discuss for 10 minutes | | | |ALLOW few groups to present and the rest to add points not mentioned | | | |CLARIFY and SUMMARIZE