Improved Tablet Production.pptx

Tablet improvement process

1. M. Pharm Sem-II Presentations Improved Tablet Production IN THE SUBJECT Pharmaceutical Management Technology IN THE FACULTY OF SCIENCE AND TECHNOLOGY Bhujbal Knowledge City, MET’s Institute of Pharmacy, Adgaon, Nashik, 422003. Maharashtra, India 1 Presented By- Shweta I. Sonawane 14 Guided By Dr. Sapna Ahirrao

2. Improved Tablet Production Tablet Production Process : Goals of Tablet Manufacturing Process To formulate tablets that are bioavailable according to indication requirements. To formulate tablets that are chemically and physically stable over a long period of time. To formulate tablets that have elegant product identity which is free from any tablet defects. 2

3. Area Required For Manufacturing Of Tablet 3

4. Techniques/ Methods used in tablet formulation Tablets are commonly manufactured by : Wet Granulation Dry Granulation Direct Compression 4

5. WET GRANULATION 5 Fig. Manufacture of Tablets by wet Granulation

6. DRY GRANULATION 6 Fig. Flow Chart of Dry Granulation

7. DIRECT COMPRESSION 7 Fig. Direct Compression Process

8. Granulation And Pelletization Equipments Granulation : Granulation is the process of collecting particles together by creating bond between them. Bonds are formed by compresson or by using binding agent. 8

9. Advancement in granulation technologies Pneumatics Granulation Freeze Granulation Technology Foamed Binder Technology Melt Granulation Technology Steam Granulation Moisture Activated Dry Granulation Thermal Adhesion Granulation Process Moist Granulation Technique TOPO Technology Continuous Flow 9

10. Steam Granulation This process is modification of conventional wet granulation. Here steam is used as binder instead of water. Advantage Uniformity distribution of the powder particles Higher dissolution rate of granules because of large surface area generated. Time saving Maintain sterility 10

11. Disadvantages Requires special equipment for steam generation and transportation Require high energy inputs Thermolabile materials are poor candidates More safety measures Required 11

12. Melt granulation Here granulation is achieve by the addition of meltable binder Binder is in solid state at room temperature but melts in the temp range 50-80°c. Melted Binder then act like a binding liquid There is no need of drying phase since dried granules are obtained by cooling it to room temperature Water soluble Binders E.g. polyethylene glycol 2000 4000 6000 8000 (40-60°c) Water insoluble Binder E.g. stearic acid (46-59°c) 12

13. Advantage Time and cost effective Controlling and modifying the release of drug Water soluble drugs are good candidates Disadvantages Heat sensitive material are poor candidates Lower melting point Binder may melt soften during handling and storage Higher melting point Binder Require high melting temp. And can contribute instability problem for heat labile material 13

14. Moisture activated dry granulation In MADG Moisture is use to activate granules formation without the need to apply heat to dry the granules Stages Agglomeration Drug is blended with diluent and powder A small amount of water is sprayed Agglomerate formation Moisture distribution absorption Moisture absorbent like microcrystalline cellulose or silicon dioxide are added while mixing Moisture redistribution within the mixture Entire mixture become relatively dry 14

15. Advantage Application to more than 90% of granulation need for pharmaceutical, food and nutritional industries Time efficient Suitable for continuous processing Less energy involved during processing Disadvantages Moisture sensitive and high moisture absorbing API are poor candidates 15

16. Moist granulation technique A small amount granulation fluid is added to activate dry binder and to facilitate Agglomeration Moisture absorbing material like microcrystalline cellulose is added to absorb any excess moisture Drying step is not necessary Applicable for developing a controlled release formulations 16

17. Thermal adhesion granulation process It Is Applicable for preparing direct tableting formulations Mixture of API and excipients are heated to a temp 30-130°C, in a close system until granulation It provides granules with Good flow property Binding capacity to form tab of low friability Adequate hardness 17

18. Foam granulation Time efficient Cost effective IR, CR formulation Water sensitive drugs Uniform binder distribution No overwriting 18

19. Freeze granulation technology By spraying a powder suspension into liquid nitrogen the drops are Instantly frozen. In a subsequent Freeze drying the granules are dried by sublimation of the ice without any segregation effect. Finally it produces spherical, free flowing granules . 19

20. TOPO technology It requires very small quantity of liquid to start the chain reaction Pure water or water ethanol mixture are used. Technology produce granules for tablet which contains at least one solid crystalline, organic acid and one alkaline or alkaline earth metal carbonate that react with the organic acid in aqueous solutions to form carbon dioxide. As the result there is no solvent residue in the finish product, granules have excellent hardness and stability. 20

21. Continuous Flow Technology The technology dose not need any liquid to start the chain reaction Granulation is carried out in an inclined drum into which powder is fed at one end and granulate is remove at other. The process produces granules with surface protected by inactive components that do not harm to sensitive API. CF technology can produce up to 12 tones of granules every day. 21

22. Pelletization It is an Agglomeration process that converte fine powder or particles of bulk drug and excipients into small free flowing more or less spherical unit and called pellets. Advantages of pellets Improved appearance of product. Improved flow properties and ease of packing resulting in uniform and reproducible fill weight of tablets and capsules. Improved safety and efficacy of active ingredient. Decreased handling hazards and easier transport. Pelletization can be used for taste masking of unpalatable drugs. 22

23. Disadvantages of pellets Pellets are rigid and so cannot be pressed into tablets,So they have to be encapsulated into capsules. The production of pellets is quite an expensive process due to the requirement of highly specialized equipment and trained personnel. The control of production process is difficult. (e.g. the amount of water added and time is critical for the quality of pellets as over-wetting can occur very easily.) Pelletization Techniques 1. Pelletization by extrusion spheronization 2. Drug layering (dry powder layering & solution and suspension layering) 3.Cryopelletization. 4. Freeze pelletization 5. Globulation 6. Compression 7. Balling 23

24. Extrusion-Spheronization The method involves the following main steps The dry mixing of the ingredients, in order to achieve homogenous powder dispersions; Wet massing, in which the powders are wet mixed to form a sufficiently plastic mass. An extrusion stage, in which the wet mass is shaped into cylindrical segments with a uniform diameter The spheronization stage, in which the small cylinders are rolled into solid spheres (spheroids) The drying of the spheroids, in order to achieve the desired final moisture content Screening (optional), to achieve the desired narrow size distribution 24

25. Extrusion Extrusion consists in applying pressure to a wet mass until it passes through the calibrated openings of a screen or die plate of the extruder and further shaped into small extrudate segments. The extrudates must have enough plasticity in order to deform, but an excessive plasticity may lead to extrudates which stick to each other. The diameter of the segments and the final size of the spheroids depend on the diameter of the openings in the extruder screen. 26

26. Spheronization Spheronization refers to the formation of spherical particles from the small rods produced by extrusion. The essential part of the spheronizer is the friction plate. The indentation pattern on the plate can have various designs, which correspond to specific purposes. In order to form spheroids, the extrudates are brought onto the rotating friction plate of the spheronizer , which imparts a rolling motion to the material. Following the collisions between the extrudates with each other and with the friction plate and the stationary walls of the spheronization chamber, the cylindrical segments change their shape and size. Themovement of the product along the chamber and transition from the almost cylindrical segments to spheres during the spheronization process occurs in several stages 27

27. Drug Layering In powder layering method, the binding liquid helps in forming successive layers of dry powder of drug and other components on starting cores by forming liquid bridges which are eventually replaced by solid bridges. In order to achieve the desired pellet size, successive layering of drug and binder solution is continued. The first equipment used to manufacture pellets on a commercial scale was the conventional coating pan, but it has significant limitations as pelletization equipment. The degree of mixing is very poor, and the drying process is not efficient. Other equipments used for powder layering process are: Tangential Spray granulator Centrifugal Fluid Bed granulator. 28

28. Cryopelletization Cryopelletization is a process whereby droplets of a liquid formulation are converted into solid spherical particles or pellets by using liquid nitrogen as the fixing medium at -160°C . The procedure permits instantaneous and uniform freezing of the material. The rapid heat transfer that occurs between the droplets and liquid nitrogen is responsible for the same. The pellets are dried in conventional freeze dryers. Generally, 3-5 kg of liquid nitrogen is required for preparation of 1 kg pellets. 29

29. Compression Compression is one of type of compaction technique for preparing pellets. Pellets of definite sizes and shapes are prepared by compacting mixtures or blends of active ingredients and excipients under pressure. The formulation and process variables controlling the quality of pellets prepared are similar to those used in tablet manufacturing. Balling Balling is the pelletization process in which pellets are formed by a continuous rolling and tumbling motion in pans, discs, drums or mixers. The process consists of conversion of finely divided particles into spherical particles upon addition of appropriate amounts of liquid 30

30. Continuous and Batch mixing Batch mixer Ingredients are loaded into the mixer processed until the powder is homogeneous and then discharge as a single batch. Mixing a new batch requires repeating these steps perhaps with additional intermediate steps for cleaning the mixer between the batches because batch mixing is a sequential process the output is measured in kg /batch Several types of batch mixers are available are as follows Tumbler Blender - Double Cone Blender, V Blender Convective Mixer- Ribbon Blender, Paddle Blender, Planetary Mixer Fluidization Blender- Double Paddle Mixer 31

31. Continuous mixers An uninterrupted steam of ingredients flows into the mixer from above. Ingredients are processed as they travel through the mixer and continuous steam of homogenized powder flows out of discharge nozzle. Every stage of continuous flow process take place continuously and simultaneously within a specified time frame and so their output is measured in kg/hr. Continuous mixing equipment Barrel Type Continuous Mixer Zigzag Type Rotating Shell With Rotating Blade 32

32. Rapid Mixing Granulator RMG is used in pharmaceuticals to make granules. The components of the RMG (impeller and chopper) are highly responsible for the   wet granulation  process. Working principle of RMG: Rapid mixture granulator works on agitation, tumbling. The impeller is responsible for uniformly mixing wet granules, and the chopper helps in a break or reduced particle size. At the starting process or during binder addition, the impeller and chopper generally operate at low speed. Then after the formation of wet mass, they are operated at high speed to make the desired granule size.

33. A dvantage: Easy to operate . Required less time for clean and easy to clean Safety is adequate Standardized according to  GMP Self-discharge Mixing can be performed at a large scale at less time Can produce Homogenous mass and later on granules in less time. Disadvantage: High noise level Required large space to install During the process, temperature becomes high because of friction force between granules. High in cost Working height is more, so it requires more effort to add materials .

34. Conclusion It can be concluded that due to their good technological and biopharmaceutical advantages, tablet improvement has gained and importance in modern pharmaceutical science and are expected to play a major role in design and fabrication of many novel granulation and pelletization techniques in the future. Influence of process improvement on minimizing process time, labor and cost reduction performance. 36

35. Referance Roop k Khar, SP Vyas, Farhan k Jain. Lachman/Liberman’s the theory and practice of industrial pharmacy. CBS publisher& distributor pvt ltd, 2013.
Michael E. Aulton, K. M. (n.d.). Aulton’s pharmaceutics the design and manufacture of medicines. Churchill Livingstone Elsevier. 37