Lyophilisation technique.ppt
- 1. M. Pharm Sem-II Presentations LYOPHILISATION SUBMITTED TO SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE FOR PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF MASTER OF PHARMACY IN THE SUBJECT Pharmaceutical manufacturing technology IN THE FACULTY OF SCIENCE AND TECHNOLOGY Bhujbal Knowledge City, MET’s Institute of Pharmacy, Adgaon, Nashik, 422003. Maharashtra, India Academic Year- 2021--2021 1 Presented By- Mr.Krishna Khamkar Guided By- Dr.S.P.Ahirrao
- 2. Content • Definition • Principle • Process • Avdantages • Disavantages • Application • Conclusion • Reference 2
- 3. Definition • A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation and then desorption to values that will no longer support biological activity or chemical reactions. 3
- 4. Principle • Freeze drying or lyophilisation is the removal of ice or other frozen solvents from a material through the process of sublimation and the removal of bound water molecules through the process of desorption. • Lyophilisation is performed at temperature and pressure condition below the triple point,to enable sublimation of ice. • The entire process is performed at low temperature and pressure by appling the vaccum. • The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during the lyopholisation. • Sublimation of water can take place at pressures and temperature below triple point i.e. 4.579 mm of Hg and 0.0099 degree Celsius. 4
- 5. Cont… 5 At atmospheric pressure (approx. 1,000 mbar) water can have three physical states Solid; Liquid; Gaseous. Below the triple-point (for pure water: 6.1 mbar at 0°C), only the solid and the gaseous states exist Phase diagram of water
- 6. Steps involved in lyophilisation Freezing drying • Step 1 Primary drying • Step 2 Secondary drying • Step 3 6
- 7. Process • Pretreatment / Formulation • Loading / Container (ex. Flask, Vials) • Freezing at atmospheric pressure • Primary Drying (Sublimation) under vacuum • Secondary Drying (Desorption) under vacuum • Removal of Dried Product from Freeze Dryer 7
- 8. Freeze drying(solidification) • Freezing the product solution to a temperature below its eutectic temperature. • Low temperature and low atmospheric pressure are maintained. • The rate at which your sample freezes will affect the size of the ice crystals that form. If not done properly, it can impact the speed of reconstitution, length of the freeze-drying process and integrity and stability of your sample. • Unfrozen product may expand outside of the container when placed under drying with high vaccume. • Slower cooling results in large ice crystals and less restrictions channels in the matrix during the drying process. 8
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- 10. Primary drying (sublimation) • Sublimation is when a solid (ice) changes directly to a vapor without first going through a liquid (water) phase. • Sublimation is a phase change and heat energy must be added to the frozen product for it to occur. • Sublimation in the freeze drying process can be described simply as: 1)FREEZE - The product is completely frozen, usually in a vial, flask or tray. 2)VACUUM - The product is then placed under a deep vacuum, well below the triple point of water. 3)DRY – Heat energy is then added to the product causing the ice to sublime. 10
- 11. • Primary drying (sublimation) is a slow process conducted at cooler temperatures, safely below the product’s critical collapse temperature. Sublimation requires heat energy to drive the phase change process from solid to gas. All three methods of heat transfer - conduction, convection and radiation, must be considered when freeze drying a product. • When the heat is transferred to the flask/product primarily through convection and radiation from the surrounding environment. With little control over heat flow into the product, it is more difficult to control the process. When working with products with low collapse temperatures, it may be necessary to wrap or insulate the flask to slow down the rate of heat transfer and avoid collapse. • In a shelf freeze dryer, most of the heat is transferred into the product through conduction and it is important to maximize the surface contact of the product/container/tray with the shelf. However, the effects of radiation and convection also need to be considered for product uniformity and process control purposes. • convective heat transfer can help promote uniform product drying. 11
- 12. • At the end of primary drying when all of the free ice crystals have been sublimed, the product will appear to be dried. However, the moisture content can still be in the 5-10% range due to the presence of “sorbed” water molecules attached to the product. 12
- 13. Secondary drying (Desorption) • In addition to the free ice that is sublimed during primary drying, there remains a substantial amount of water molecules that are bound to the product. • This is the water that is removed (desorbed) during secondary drying. Since all of the free ice has been removed in primary drying, the product temperature can now be increased considerably without fear of melting or collapse. • Secondary drying actually starts during the primary phase, but at elevated temperatures (typically in the 30◦C to 50◦C range), desorption proceeds much more quickly. • Secondary drying rates are dependant on the product temperature. System vacuum may be continued at the same level used during primary drying; lower vacuum levels will not improve secondary drying times. • Secondary drying is continued until the product has acceptable moisture content for long term storage. Depending on the application, moisture content in fully dried products is typically between 0.5% and 3% 13
- 14. • In most cases, the more dry the product, the longer its shelf life will be. However, certain complex biological products may actually become too dry for optimum storage results and the secondary drying process should be controlled accordingly. • During secondary drying, a “sample thief” mechanism may be used to periodically remove vials from the freeze dryer for residual moisture content determination. 14
- 17. Advantages of Lyophilisation • Thermolabile materials can be dried. • Prolonged shelf life. • Freeze drying takes place at very low temperature so the decomposition of substance is minimized. • Stability of the product maintained. • Compatible with aseptic operations. • Minimal loss in volatile chemicals and heat-sensitive nutrient and fragrant components. • Minimal changes in the properties because microbe growth and enzyme effect can not be exerted under low temperature. 17
- 18. Disavdantages • Volatile compounds may be removed by high vacuum. • Single most expensive unit operation. • Stability problems associated with individual drugs. • Some issues associated with sterilization and sterility assurance of the dryer chamber and aseptic loading of vials into the chamber. • Long time process • Many biological molecules are damaged by the stress associated with freeze-drying . 18
- 19. Lyophilised pharmaceutical products Sr. No. LYOPHILIZED PRODUCTS PER VIAL THERAPEUTIC CATEGORY 1 ACETAZOLAMIDE INJECTION 500MG / VIAL Anti-glaucoma 2 ACYCLOVIR INJECTION 250MG/VIAL, 500MG/ VIAL, 1GM/VIAL Antiviral 3 AMPHOTERICIN INJECTION 50MG/VIAL, 100MG/VIAL Antifungal 4 PHENYTOIN INJECTION 50MG/ML Anticonvulsant 5 AZITHROMYCIN INJECTION 500MG/VIAL Antibacterial Antibiotic 6 CASPOFUNGIN INJECTION 50MG/VIAL, 70MG/VIAL Antifungal 7 CLARITHROMYCIN INJECTION 500 MG/VIAL Antibiotic 8 COLISTIMETHATE INJECTION 100,000 IU / VIAL, 200,000 IU/VIAL Antibiotic 9 DOBUTAMINE HCL INJECTION 50MG/ML, 250MG/VIAL Cardiac 19
- 20. Applications • In food industry • In pharmaceuticals and biotechnology • Other industries 20
- 21. Conclusion • The lyophilization technique proved to be an advantage for enhancing the stability of the product because the moisture content of the formulation is greatly reduced. • In the freeze dried solid state, chemical or physical degradation reactions are inhibited or sufficiently decelerated, resulting in an improved long term stability • Shelf life of the product is increased due to lyophilisation process • The size of the product is also reduce and ease for the transportation. 21
- 22. Reference • The theory and practice of industrial pharmacy by Leon Lachmann, Herber Liberman and joseph kanig.1991.pg no-62-64, 672-674 • Aultons pharmaceutics- The design and manufacture of medicines by Micheal E.Aulton,2009 pg 195. • https://www.spscientific.com/freeze-drying-lyophilization-basics/ • https://www.researchgate.net/publication/292047227_LYOPHILIZATION_ FREEZE_DRYING_-_A_REVIEW 22