1. Presentation by:k.ManasaRoll no-256212886046M.Pharmacy(pharmaceutics)1

2. CONTENTS DEFINITION ADVANTAGES SPHERONIZATION PROCESS EXTRUSION ROTOR GRANULATION KEY SPHERONIZATION FACTORS MACHINE PARAMETERS PRODUCT PARAMETERS REFERENCE2 3. Definition:- Spheronization or marumerization, is a rapid and flexibleprocess where pharmaceutical products are made into smallspheres, or spheroids of diameter ranging from about 0.5mm to1mm where as in marumerizatin 0.6mm t0 1.2mm.3 4. Advantages:-1. Optimum flow and handling characteristics:- The flow characteristics of spheres makes them suitablefor transportation by most systems found in thepharmaceutical industry, including vacuum transfer.2. More reproducible packing into small container:- The packing into small containers, such as hard gelatinecapsules, or larger packages is much more convenient thanother drug form such as powders or granules. Eliminate quality problems with variable dosage due topacking problems with powder.4 5. 3. Minimum surface area/volume ratio:-Spheres provide the lowest surface area to volumeratio and thus pharmaceutical compounds can be coatedwith minimum of coating material. Important for effectiverelease of some drugs.4. Optimum shape for coating and for controlledrelease:-Coating can provide controlled, targeted release atdifferent location within the body.spheres are dense material that can easily be coatedwithin a minimum of coating material.5 6. 5.Easy mixing of non-compatible products:- spherical particles are easily mixed.6.Elimination of dust:- Contamination is reduced. The amount of fines and dust will be reducedduring transport and handling.7.Improve hardness and friability:- Spheronization increases the hardness and reducesfriability of granules.6 7. Spheronization process Dry mixing of ingredients to achieve a homogeneous powderdispersion; Wet massing to produce a sufficiently plastic wet mass. Extrusion to form rod shaped particles of uniform diameter . Spheronization to round off these rods into spherical particles . Drying - to achieve the desired final moisture content. Screening -to achieve the desired narrow size distribution.7 8. 8 9. Extrusion It produces rod shaped particles of uniform diameter from thewet mass. Wet mass is forced through the dies and shaped into smallcylindrical particles with uniform diameter . The extrudate particles breaks at similar lengths under thenown weight. Extrudate must have enough plasticity to deform ,but extrudateparticles do not adhere to other particles when collected. Based on their feed mechanism extruders divided into 3 types1.screw feed extruder(axial and radial)2.Gravity feed extruder (cylinder roll, gear roll and radial)3.Piston feed extruder9 10. 2. Screen or basket extruder:- Lower density extrudate. Relatively high throughput.3. Gear extruder:- produces relatively high density. Gears are robust and long lasting.101.Screw feed extruder:-Commonly used in industrialapplication.High pressure and heat can degradepharmaceutical product. 11. Type of extruder used in pharmaceutical industry:-Equipment Description Main usesExtruder 20 Bench top screenextruderLaboratory experimental/smallscale production(25-30kg/hr)Extruder 35 Production screenextruderLab /production , low cost.high out put (2kg/min) of lessdense extrudate.Extruder 40 Production gearextruderQuality extrudate output 40-100kg/hrExtruder 100 Production gearextruderQuality extrudate output100-500kg/hr11 12. 1.Extruder 20:- Designed for pharmaceuticalprocess development workin lab. Few dead spaces wherematerial can collect. Minimum effective loadrequirement is about 30g Can be easily dismantled foreasy cleaning.12 13. Extruder 35:- Extruder 40:-13 14. The mini screw extruder:- For small quantity of material. Smallest batch size can be extrudedis about 5g. Material loaded into it manually. Die hole size is 0.7mm to 2mm. Minimum wastage of valuableproduct. Can be quickly dismantled for easycleaning.14 15. The primary extrusion process variables are :1) The feed rate of the wet mass2) The diameter of the die3) The length of the die4) The water content of the wet mass15 16. THE SPHERONIZATION PROCESS:-Basic configuration:- Machine consists of a rotating friction disk,designed to increase friction with theproduct, which spins at high speed at thebottom of cylindrical bowl.16 17. The ongoing action of particles colliding with the wall and beingthrown back to the inside of the plate creates a rope-likemovement of product along the bowl wall. When particle have obtained the desired spherical shape,discharge valve of the chamber is opened and the granules aredischarged by the centrifugal force.17 18. The rounding of the extrudate into spheres is dependent onfrictional forces generated by particle- particle and particleequipment collisions. The bottom disc has a grooved surface to increase theseforces. Two geometric patterns are generally used.1) A cross hatched pattern with grooves running at rightangles to one another .2) A radial pattern with grooves running radially from thecentre of the disc.18 19. The transition from rods to spheres during spheronizationoccurs in various stagescylindercylinder with rounded endsdumbbelleclipsedspheres19 20. Rotor granulation In the fruend granulator ,the powder mix is added to thebowl and wetted with granulating liquid from a spray. The baseplate rotates at high speed and centrifugal force,keeps the moist mass at edges of the rotor. The velocity difference between the rotor and the staticwalls, combined with the upward flow of air around therotor plate ,cause the mass to move in a toroidalmotion,resulting in the formation of spheres.20 21. 21Fruend granulator 22. Standard features of marumerizer Perfect cGMP design,smooth covering. Explosion free design. Automatic cleaning of entire system. Completely integrated full opening side discharge. Advance process for easy and automated granulation. jacketed/insulated bowl. Integration with mill is possible. Video monitoring the process.Technical specifications for marumerizer:22Model Marumerizer-380Marumerizer-500Marumerizer-700Marumerizer-900Marumerizer-700(T)Marumerizer-900(T)Batchcap./kgs.0.5-3.2 3-10 5-20 15-50 10-40 30-100 23. 23Marumerizer QJ-1000T Spheronizer 24. Table summarizing the different types of calevaspheronizers for pharmaceutical production anddevelopment :Equipment Description Main useMicro spheronizer --------- Laboratory:smallquantitySpheronizer-120 Bench top Laboratory/experimentalSpheronizer-250 Lab scale bench top Low cost high outputSpheronizer-380 ------ Quality spheroids outputSpheronizer-500 ------- Quality spheroids output24 25. Example of spheronizers:- Spheronizer 250:-25Spheronizes380spheronizer500 26. Key spheronization factors:-1.Disc speed and load.2.Disc groove geometry.3.Disc diameter and speed.4.Product parameters.5.Retention time.1.Disc speed & load:- There is an optimum disc speed and load for each discdiameter.Momentum too low:- Extrudate not densified sufficiently. No spheres formed.26 27. Momentum too high:- Too much force on the granules. Compression of particles within the granules. Minimum porosity. Granules fracturing.The spheronizer drum charge volume:- The optimum charging volume depends upon the machine sizeand the product characteristics. Ex-machine with a 380nm diameter disc, charged with a volumeof 4 liters. Depending on the density of the spheres andsmoothness of the granules.27 28. 2.Disc groove geometry:- Square cross hatched design is most commonly used.3.Product parameter:- The particles must be plastic enough to allow deformationduring collisions, but also must be strong enough towithstand collision with the disc, other particles & thespheronizer wall without breaking up.4.Retention time:- Typical spheronization retention time necessary toobtained spheres is from 2 to 6 min .28 29. Machine parameters The basic machine consist of a round disc with rotatingdrive shaft ,spinning at the bottom of a cylindrical bowl. This is most often cross hatched ,several sizes available. These discs are designed to increase the friction with theproduct.1)Friction plate pattern2)Friction plate speed3)Retention time4)The charge volume29 30. 1)Friction plate pattern:- The most common groove pattern used for spheroniser discs isthe waffle-iron or cross hatch design ,where the friction plateis like a chessboard of chopped off pyramids. Discs with a radial design are also used.2)Friction plate speed:- The typical rotation speed of a 700 mm diameter disc rangesfrom 400 to 500 rpm. The optimum speed depends on the characteristics of theproduct and the particle size.30 31. 3)Retention time:- Typical retention time to obtain spheres range from 2 to 6minutes. The edges of cylindrical granules are the most fragile part andthey will generate dust during handling . Spheronization with short retention time can help to reducedust significantly.4)The charge volume:- The optimum level depends upon the machine size and theproduct characteristics. Increasing the load per batch increases the hardness of thespheres and smooths the granule surface.31 32. Product parameters The rheology of the product can be changed by varyingthe formulation or physically. Binders can be used to increase the strength of thegranules and reduce the amount of fines generatedduring the process. Lubricants will increase the plasticity. Water can also be used as lubricant. The optimum moisture content for spheronization isslightly less than for extrusion.32 33. 1)Auxillary equipment:- These can help to improve the efficiency and ease of theprocess.2)Water jacket:- Warm water useful to drive off moisture that would causeproduct sticking on the chamber wall. Cooling the wall will avoid temperature rises in heatsensitive products. The average temperature rise is generally rathersmall(normally about 4 c).33 34. 3)Air introduction:- It prevents dust from getting between the rotating plateand the wall of the chamber . It also help to remove moisture from the granules surface.4)Non- stick coatings :- The chamber wall and the spheronization plate can becoated with non-stick materials if this is necessary forease of use with sticky materials or cleaning.34 35. Reference The design and manufacture of medicines (edited byMichael.E Aulton),3rd edition.Aultons(pharmaceutics)page no:419-422. Inventi rapid:pharma tech journal ;review on extrusionand spheronization (publication date 20-10-2012). A literature review .,Chris Vervaet,Lieven Baert and JeanPaul Remon.Interntional journal of pharmaceutics volume116(28th march 1995). www.umangpharmaceuticals.com.35 36. ge THANK YOU36