Validation of dissolution apparatus


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This Presentation is about How to Validate Dissolution Apparatus,about the qualifications to be accepted or not.How to design dissolution study.

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Validation of dissolution apparatus

  1. 1. Presented By- Miss S. M. Kumbhar Under the Guidance of- Dr. A. S. Kulkarni 1
  2. 2. VALIDATION History-  Concept of validation was first proposed by FDA officials in 1970, by Ted Byers & Bud Loftus.  Concept was first develop for equipment and process. 2
  3. 3. REASONS FOR VALIDATION  To improve Quality of Pharmaceuticals  To design system properly to provide high degree of assurance. 3
  4. 4. VALIDATION Validation is process of establishing documented evidence that provides high degree of assurance that specific process will consistently produce a product meeting its predetermined specifications and quality. 4
  5. 5. Validation Equipment Validation Facilities Validation HVAC Validation Cleaning validation Process validation Analytical Method Validation Computer System Validation 5
  6. 6. DISSOLUTION  Process by which known amount of drug substance goes into solution per unit time under standardized conditions.  Primary goal- to provide measurements for bioavailability & to demonstrate bioequivalence from batch to batch. 6
  7. 7. NEEDS OF DISSOLUTION TESTING 1. To ensure continuity of product quality & performance of manufacturing process 2. Requirement for regulatory approval for product marketing Dissolution testing is conducted using dissolution test apparatus 7
  8. 8. Validation of dissolution test apparatus. Why??? 8
  9. 9. To have a high degree of assurance dissolution apparatus should be consistence and accurate in its performance. Therefore validation of this equipment is required. . Validation of Dissolution Test Apparatus9
  10. 10. QUALIFICATION To ensure that equipment is fit for intended purpose, there are no. of qualifying steps that vendor / analyst should apply to analytical instruments. Equipment is evaluated through these tests & successful completion justifies instrument operates and performs 10
  11. 11. Fig.No.1 Steps of Qualification11
  12. 12. DESIGN QUALIFICATION When developing dissolution method DQ is built into apparatus selection of process, Dosage form & delivery system will determine choice of equipment. Example-first choice for beaded product may be USP app 3…… as it is designed to confine beads in a screened-in cylinder. 12
  13. 13. INSTALLATION QUALIFICATION Used to verify that instrument has assembled in the appropriate environment & its functioning according to predefined set of limit. Example- Setting up fully automated dissolution testing apparatus requires: proper plumbing, hot water source, stable bench top. 13
  14. 14. OPERATIONAL QUALIFICATION During this qualification analyst or vendor assess that equipment works as specified & generates documented data. Example- For dissolution water bath temperature, shaft rpm speed would be obvious operational parameters 14
  15. 15. PERFORMANCE QUALIFICATION This is conducted to ensure that system is in normal operating environment & performing designed set of tasks within the specifications. Example- Centering, wobble, height of paddle or basket attached to shaft, speed, temperature 15
  16. 16. DISSOLUTION TEST APPARATUS NON - COMPENDIAL COMPENDIAL NON –COMPENDIALEQUIPMENTS: Rotating bottle, mini paddle, mega paddle, beaker method, peak vessel, diffusion cells, chewing gum apparatus etc. COMPENDIAL EQUIPMENTS: USP Apparatus 1-7 16
  18. 18. COMPENDIAL EQUIPMENTS Apps. No. USP IP 1 Rotating basket Paddle assembly 2 Paddle Assembly Rotating basket 3 Reciprocating cylinder 4 Flow through cell 5 Paddle over disk 6 Cylinder 7 Reciprocating holder 18 Table No. 1 Compendial Equipment
  19. 19. QUALIFICATION OF NON-COMPENDIAL EQUIPMENT If equipment is commercial product IQ and OQ can be obtained from the equipment vendor which includes vendor specification and tolerances for equipment. But if equipment is in-house design then process becomes difficult. We have to look at adjustments & moving parts, obtain operational parameters i. e. agitation rate, flow rate, 19
  20. 20. METHODS A] Calibration  Non-compendial & some compendial apparatus do not have calibrator tablets, in some case in house calibrator tablets are designed.  Some unique aspects of equipment can only be detected with USP calibrated tablets, there are no practical measuring tools available for analyst. e.g. vibration and vessel irregularities. 20
  21. 21. B] HYDRODYNAMICS Dissolution fluid flow should be free from irregularities or variable turbulence. Highly variable data may be unsuitable for that product. C] OTHER CONSIDERATIONS- Ruggedness should be thoroughly evaluated before considering transferring product testing to another site.21
  22. 22. APPARATUS SUITABILITY TEST • Used calibrator tablets • Duration of apparatus suitability test a) NLT twice a year per equipment b) After any equipment change c) After significant repair d) After movement of assembly 22
  23. 23. QUALIFICATION OF COMPENDIAL EQUIPMENT A. Calibration or apparatus suitability test: Calibrator tablets are required B. Heating jacket C. Peak vessel D. Clip & clip less baskets E. Sinkers F. Deaeration G. Automated sampling H. Single entity with two part detachable shaft design 23
  24. 24. PEAK VESSEL  Designed to eliminate mounding or coning by having a cone molded into the bottom of glass vessel.  Used when product contains dense excipients that have tendency to cone. Fig.No.2 Peak vessel 24
  25. 25. Clip And Clip Less Basket  These two types of basket designs are commercially available.  As prednisone calibrator tablet showed higher dissolution rate with three pronged apparatus it’s the official design of USP. Fig.No.3 Basket attachment designs Left: : o ring Right : three pronged 25
  26. 26. Drawbacks of O Ring And Three Pronged Apparatus Design O ring design  In Robotic dissolution tester, robotic arm can remove o ring type basket more efficiently  Gives different results than 3 pronged apparatus Three pronged apparatus design  Clips disturbs the fluid flow in the vessel  Can weaken overtime  Causes basket to attached too loosely to shaft & increases the wobble 26
  27. 27. SINKERS  Used for sticking or floating of dosage forms  Many other sinkers are available commercially  Validated sinkers are used, any of the design could be consider Hand made sinker Sinker required in Japanese pharmacopoeia 27Fig.No.4 Sinkers
  28. 28. DEAERATION  Designed to remove air bubbles.  Mechanism: Thin film vaccum is used, preheated media is sprayed using spray- disbursing nozzle into closed vessel, vaccum is applied to remove gases. Fig.No.5 Deaeration equipment 28
  29. 29. Automated Sampling shaft prefilter Fig.No.6 Automated sampling with hollow shaft 29
  30. 30. ROTATION SPEED STUDY  This study should be conducted during OQ  Study includes measurement of speed of shaft rotation.  Speed should be measured with photo tachometer for 30 mins.  Speed of shaft rotation should be verified to be within 4% of speed specified in monograph. 30
  31. 31. TEMPERATURE DISTRIBUTION STUDY  Study should be conducted during OQ  Includes temperature mapping of each vessel  Temp. should be mapped by using data acquisition system for minimum time as per monograph/1hr.  Temperature of apparatus 1, 2, 3, 4 = 370 c ± 0.50 c  Temperature of apparatus 5, 6 = 320 c ± 0.50 c 31
  32. 32. SOURCES OF ERRORS 1. Drug substance properties 2. Drug product properties 3. Equipment 4. Method consideration 5. Observation 6. Automation 7. Cleaning 8. Method transfer 32
  33. 33. SOURCES OF ERRORS A] Drug substance properties e.g. Solubility, pH B] Drug product properties Mechanical, formulation C] Equipment Mechanical & chemical aspects, Apparatus suitability test D] Method consideration To avoid errors Film coated tablets-sticky-sinker Suspension-syringe/pipette/beaker Medium-volume difference Presence of surfactants 33
  34. 34. SOURCES OF ERRORS E] Observation Sinkers-turns of wire helix-its effect Manual sampling F] Automation Problems-disconnection, inadequate cleaning, mix-ups G] Cleaning Many products, same equipment major source of error H] Method transfer Sinkers, dispensing apparatus, sampling methods, precise medium, standard preparations, grade of reagents should be uniform. 34
  35. 35. CONCLUSION At the conclusion acceptable OQ, IQ, PQ, DQ the dissolution apparatus is considered, validated and acceptable for use to perform dissolution testing. 35
  36. 36. REFERENCES • Abdou H. M. (1989). Dissolution, Bioavailability & bioequivalence (pp.5-33,73-100). Easton Pennsylvania: Mack publishing company. • Ansel H. C., Popovich N. G.,& Allen L. V. (2010). Pharmaceutical Dosage Forms and Drug Delivery Systems (pp.151-153) Baltimore, Maryland: Lippincott Williams. • Dressman J., & Kraimer J. (2005). Pharmaceutical dissolution testing (PP.39-67) Singapore, New York: Taylor & Francis Group. • Frost S. M. A. (2004, Feb).Introduction to validation of Dissolution apparatus (pp.19-21).Dissolution technology. • Indian Pharmacopoeia (2007). Government of India, Ministry of Health and Family welfare (vol -I, 179-181), Ghaziabad: The Indian Pharmacopoeia Commission 36
  37. 37. REFERENCES • Lachman L., Lieberman, & Kanig (2009).Theory and Practice of Industrial Pharmacy (pp. 301-303,832-833), CBS Publishers & Distributors. • Martin A (1991). Physical Pharmacy, physical chemical principles in pharmaceutical science (pp.352, 408-412), Mumbai: K. M. Varghese company. • Nash R. A., Berry I. R. (3rd ed). Pharmaceutical process validation, Peither T. L., Equipment and facility (vol-129, pp.443-463). New York: Marcel Dekker. • The United States Pharmacopeia National Formulary ( USP 24, NF 19). Twinbrook parkway, Rockville: United States Pharmacopeia Convention (pp.1941-1943) 37
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