Industrial pharmacy PHT - 432

1. SALMAN BIN ABDULAZIZ UNIVERSITY COLLEGE OF PHARMACY Industrial pharmacy PHT - 432 Mohammad Khalid Anwer, Ph.D e-mail:-mkanwer2002@yahoo.co.in

2. INDUSTRIAL PHARMACY TERMINOLOGY • 1- Material: • A term used to cover starting materials, • intermediate products, packaging materials • and finished products • 2- Starting Material: • Any substance used in the manufacture of a medicinal • product excluding packaging materials. • 3- In-Process Material: • Means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in the preparation of the drug product.

3. 4- Packaging Material : Any material used in the packaging of a product. It does not normally include the outer packaging or transit cases used for departmental transportation or shipment of orders. (a)Primary Packaging Material: Which is in direct with medicinal product. (b) Printed Packaging Material: A packaging material which is imprinted with a text.

4. 5- Active Ingredient: Means any component that is intended to give pharmacological activity. 6 - Inactive Ingredient : Means any component other than an "active ingredient" . 7- Dosage Form: Refers to the physical form in which a drug is administered to or used by a patient.

5. 7- Intermediate Product: A partly processed material which must undergo further processing before it becomes a finished product. 8- Drug Product: A dosage form containing one or more active therapeutic ingredients along with other substances included during the manufacturing process.

6. 9- Finished Product: A medicinal product which has completed all stages of manufacture, including packaging. 10- Batch: Means a specific quantity of a drug and/or other material that is intended to have uniform character and quality, within specified limits , and is produced according to a single manufacturing order during the same cycle of manufacture.

7. 11- Lot : A batch It is a specific identified amount produced in a unit of time or quantity in a manner that assures uniform character and quality within specified limits. 12- Lot Number: "Control Number, or Batch Number" Means any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined.

9. 13- "Manufacture, Processing, Packing or Holding of a Drug Product“ • Includes packaging and labeling operations, testing, and quality control of drug products. • 14- Strength : • The concentration of the drug substance (weight/weight, weight/volume, or unit dose/volume basis). • The potency, that is the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (expressed, in terms of units by reference to a standard).

10. 15- Storage : The term is applied for safe keeping of material and drug products in drug stores, Pharmacies, hospitals ...etc. under the specified conditions. • 16- Storage Conditions: • The conditions specified for storing • The product (Temperature, humidity, • container etc.)

11. 17- Stability : • The stability of a pharmaceutical preparation is: • its degree of resistance to chemical and • physical changes. • The efficacy of the preparation must remain • constant (or change only within the limits • specified by legal provisions) until the date of • expiration. • 18- Stability Indicating Assay : • The assay which is sensitive and selective too • determine quantitatively the active ingredient • in the presence of its decomposition products.

12. 19- Shelf-Stability : The stability of the drug or drug product at ambient room temperature (15-35°C). 20- Overage : The excess quantity of drug that must be added to the preparation to maintain at least 100% of' the labeled amount during the expected shelf-life of the drug.

13. 21- Expiration Date : The date placed on the container label of a drug product that designates the date through which the product is expected to remain within specifications. If the expiration date includes only a month and a year, it is expected that the product will meet specifications through the last day of the month. Kinetically it is the time required for 10% of the material to disappear.

14. 22- Accelerated Testing :(Stress Testing) Studies designed to increase the rate of chemical or physical degradation of a drug substance or drug product by using exaggerated storage conditions. The purpose is to determine kinetic parameters, if possible, and/or to predict the expiration dating period.

15. 23- Temperature Control: All Temperatures in Degrees. (a) Cold Place: The temperature does not exceed 8". (b) Refrigerator: The temperature is thermostatically controlled between 2° and 8° . (c) Freezer: The temperature is thermostatically controlled to not higher than - 10 °. (d) Cool Place: The temperature is between 8 ° and 15 °. (e) Warm Place: Any temperature between 30 ° and 40 ° (f) Room Temperature: The temperature is between 15 ° and 30 ° . (g) Excessive Heat: Any temperature above 40 °.

16. 24- Good Manufacturing Practice (GMP) : • That part of quality assurance aimed at ensuring that products are manufactured, to a quality appropriate to their intended use. • 25- Quality: • The ability of a drug product to satisfy the • users need.

17. Introduction to Industrial Processing • The emphasis in making pharmaceutical preparations has moved from the individual dispenser to the large-scale manufacturer. • Reasons for Increasing Large-scale Manufacture • Economic Reasons • Accuracy • Greater Scope

18. Economic Reasons As the scale of manufacturing batches increases, the cost of production decrease. Accuracy The larger the quantities of materials involved, the accuracy of measurements increased, with laboratory control during manufacture and testing the final product. Greater Scope The increasing complexity of modern therapy has made it impossible to prepare many medicaments on a small scale as antibiotic production is possible only on a large scale.

19. Pilot Plant Scale-Up Techniques In the pilot plant, a designed formula is transformed from being manufactured on a laboratory scale, or in intermediate-sized pilot plant equipment into a viable, full-bodied product by the development of a reliable and practical method of manufacture that effects the orderly transition from laboratory to routine processing in a full-scale production facilities with high-speed production equipment in a cost-effective manner

20. General Considerations in Pilot Plant Studies: • A close examination of the formula to determine its ability to withstand batch-scale and process modification. • A review of a range of processing equipment to determine which would be the most compatible with the formulation as well as the most economical and simple in producing the product.

21. During this process some considerations must be determined: • The availability of raw materials to meet the specifications required. • Production rates and their relationship to immediate and future market requirements. • The physical space required and the arrangement of related functions. • The requirements, training, reporting relationships and responsibilities of personnel.

22. PERSONNEL REQUIREMENTS • Personnel in the pilot plant must has the following the qualifications requirements: • Be aware of the meaning of the formulator. • Understand the view of production personnel. • Level of scientific education. • Pharmaceutically trained scientists know the interrelationship between pharmaceutical processes and the chemical, physical, biochemical, and medical attributes of dosage forms. • Some engineering capability . • Knowledgeable in both electronics and computers.

23. Space Requirements • A pilot plant has the following four types of space requirements. • Administration and Information Processing. • Physical Testing Area. • Standard Pilot Plant Equipment Floor Space. • Storage Area.

24. Administration and Information Processing. Office and desk space must be provided for both the scientists and technicians. This should be adjacent to the work area But isolated to permit people to work without distractions. • Physical Testing Area. Is a working area in which samples can be laid out and examined and where physical tests on these samples can be performed.

25. Standard Pilot Plant Equipment Floor Space. • Is a separate plant space where equipment needed for manufacturing all types of pharmaceutical dosage forms is located. The area is subdivided into areas for solid dosage forms, semisolid products, liquid preparations, and sterile products.

26. Storage Area. • Separate storage area for the of active ingredients and excipients. • Storage areas for in-process materials, and material from experimental scale-up batches. • Storage for packaging materials. • Storage areas for finished bulk products.

27. Review o f the Formula The purpose of each ingredient and its contribution to the final product manufactured on small-scale laboratory equipment should be understood. Raw Materials Approval and validation of the active and excipient raw materials used in pharmaceutical products is necessary.

28. Relevant Processing Equipment The equipment that promises to be the most economical, the simplest, the most efficient, and the most capable of consistently producing product within the proposed specifications should be evaluated. Ease of cleaning should be considered, especially if multiple products are destined to be manufactured in the equipment.

29. Production Rates The immediate and future market requirements must be considered when determining the production rates. To accommodate future growth, increased production capacity may be realized more economically through more efficient utilization of smaller equipment than through purchase of oversized equipment. For example, several smaller lots produced serially (without major clean-up) may be combined in a final blend to make a single large batch.

30. Process Evaluation • The evaluation of the process critically and optimization its performance based on that evaluation. • Items that should be examined include the following: • Order of addition of components. • Adjustment of their amounts. • Mixing speed. • Mixing time. • Rate of addition of granulating agents, solvents, solutions of drugs, slurries, etc. • Heating and cooling rates. • Filter sizes (liquids). • Screen sizes (solids). • Drying temperatures. • Drying time.

31. Transfer o f Analytic Methods to Quality Assurance Proper analytic instrumentation is available and trained personnel to perform the tests. Recovery studies on the product and on placebo samples should be carried.

32. If each item of plant is represented symbolically in a diagram, the arrangement can be reduced to a simple flow sheet. Flow sheets are simplified diagrams representing the summary of the operations involved in the manufacturing processes in a number of stages with particular pieces of equipment. Material entering or leaving the process, or moving from stage to stage, is indicated by arrows.

33. Flow sheet: Purification of a substance by crystallizationwith manufacturing Processes • Storage hopper • Solvent feed • Mixing vessel (Mixing) • Filter press(Filtration) • Evaporator(Evaporation) • Centrifuge(Centrifugation)

34. Flow sheet: Manufacture of a mixed powder • with manufacturing Processes • Storage hoppers • Ball mill(Size Reduction) • (3) Sifter(Size Reduction) • (4) Powder mixer(Mixing)

35. Flow sheet: Manufacture of compressed tablets with manufacturing Processes (1) Storage hoppers (2) Granulating liquid storage tank (3) Mixer(Mixing) (4) Granulator(Size Reduction) (5) fluidized bed dryer(Drying) (6) Sifter(Size Separation) (7) Mixer(Mixing) (8) Storage hopper (9) tablet machine

36. Flow sheet: Manufacture of a dry extract • with manufacturing Processes. • drug storage hopper • water supply • (3) ethanol storage tank • (4) circulating mixer(Mixing) • (5) crushing mill(Size Reduction) • (6) extraction vessel(Extraction) • (7) extractive storage tank • (8) exhausted drug discharge • (9) steam supply • (10) Evaporator(Evaporation) • (11) vacuum oven(Drying) • (12) Sifter(Size Separation) • (13) fractionating column(Distillation)