Granulation Equipment Lecture (2) PDF

10/12/2024 Faculty of Pharmacy PHT 512 Granulation Level: 5 Fall 2024/2025 October 6th University Granulation Equipment Lecture (2) 1 2...

10/12/2024 Faculty of Pharmacy PHT 512 Granulation Level: 5 Fall 2024/2025 October 6th University Granulation Equipment Lecture (2) 1 2 1  10/12/2024 Characteristics of Granulated Materials 3 Granulation Equipment 1. DRY GRANULATION 4 2  10/12/2024 5 Dry Granulation A Three Step Process Materials are Pre-Blended, Compressed tightly together and then Milled. – Slugging Usually large compacts with variabledensity – Roll Compaction A compressed sheet of uniformdensity Fully Pre-gelatinized Corn Starch Hypromellose 6 3  10/12/2024 Granulation Equipment A) Slugging (Old Method) In "slugging" the material to be granulized is first made into a large compressed mass or "slug" typically by way of a tablet press using large flat-faced tooling. A fairly dense slug may be formed by allowing sufficient time for the air to escape from the material to be compacted. Compressed slugs are then comminuting through a desired mesh screen manually or automatically as for example by way of a comminuting mill. Formation of granules by "slugging" is also known as precompression. When tablets are made from the granulated slugged material, the process is referred to as the double compression method. Disadvantages of Slugging Single batch processing Poor process control Low manufacturing output per hour Excessive air and sound pollution, More energy and time required to produce 1 Kg of slugs than 1 Kg of roller compact. Dusty technique Aspirin Slugging 7 Granulation Equipment B) Roller Compactor Roll compaction is a method of choice for processing of moisture sensitive drugs, as no liquid binder is required in the granulation. This is suitable for compounds that either have a low melting point or degrade rapidly during heating, as the method does not involve any drying step. RCDG is useful technique for processing of drugs having low and inconsistent bulk and tap densities with very fine and inconsistent particle sizes and/or poor flow properties and poor compatibility RCDG 8 4  10/12/2024 Granulation Equipment B) Roller Compactor For Poorly Compressible Materials Often used to densify API and blends with high active loading Excellent for Moisture Sensitive Products Continuous Process, up to 600 kg/hr Granule Size is primarily controlled by the milling step Principle of compaction Roller for compaction Roller for compaction (RCDG) 9 Granulation Equipment 10 5  10/12/2024 Granulation Equipment Roll compaction is an agglomeration process in which powder (1, 4) is fed by either gravity or by means of a screw feeder (2, 3) via two equal diameter counter-currently rotating rollers. The friction between the material being processed and roller surface brings the powder towards the narrow space between the roll (nip region) (5), where the powder is subjected to high stresses leading to the formation of compact. If in-line granulator/mill system is available with the system, it will mill ribbons or briquettes into granules, otherwise densified sheets (ribbons) can be dry-sized by an oscillating mill, cone mill or impact mill (6). 11 Roller Compactors Horizontal orientation Vertical orientation Hutt Roller compactor 12 6  10/12/2024 Compaction Process During roll compaction, the powder blends are fed into the gap between two rollers (compaction zone) which Slip Zone is divided into three regions namely: 1. Slip or entry region Nip Zone 2. Nip region Nip Angle 3. Release region 13 Schematic of the main regions during roller compaction In the slip or entry region powder starts to move but at a speed slower than the roll speed. The nip region starts at a roll angle α, (nip angle), when the velocity of the powder becomes equal to that of the rolls. The powder is nipped, and densification occurs due to decrease in the gap The release region starts when the roll gap starts to increase again and its size depends on the stored elastic strains in the compact, release rate of compact, and the roll speed. 14 7  10/12/2024 Process Variables Roll speed Screw feeder speed Compaction (Roll) pressure Deaeration pressure 15 Advantages of dry granulation: Useful for heat or moisture sensitive materials. Less equipment and space than that required by wet granulation. Improve tablet disintegration since it does not involve the use of water, so it increases water-uptake ability of the disintegrant. This method is of value in the production of certain dosage forms as effervescent tablets. Disadvantages of dry granulation: Requires high duty machine if compared with direct compaction Since it is dry process, more dust is produced which may contaminate other drug When to apply Dry Granulation technique? This method is used when direct compression is not applicable (e.g., large-dose or poor compressibility drugs) When wet granulation cannot be used (e.g., drugs sensitive to heat or moisture). Vitamins and effervescent tablets are examples of products prepared by dry granulation. 16 8  10/12/2024 Granulation Equipment 2. WET GRANULATION 17 Principle of agglomeration 18 9  10/12/2024 19 Three Simultaneous Granulation Sub-Processes 20 10  10/12/2024 Granulation Equipment Low Shear granulator (Planetary mixer & Granulator) High Shear granulator (Diosna) Collette Gral mixer Fluidized Bed Granulator (FBD) 21 Planetary Mixers & Granulators 1 Planetary mixers are one of the most widely used in the pharmaceutical industry. In pharmaceutical industries planetary mixture often used for basic operations of mixing, blending, and low shear granulation. 22 11  10/12/2024 FUNCTION OF PLANETARY MIXERS 1 Mixing mechanism is shear. Shear is applied between moving blade and stationary wall. Mixing arm moves around its own axis and around the central axis so that it reaches every spot of the vessel. Consists of vertical cylinder shell which can be removed. The blade is mounted from the top of the bowl. Mixing shaft is driven by planetary gear and it is normally built with variable speed drive. 23 ADVANTAGES AND DISADVANTAGES 1 Advantages: Disadvantages: Speed of rotation can be change as per required. Mechanical heat is buildup within the More useful for wet granulation process. powder mix. Easy to cleaning and discharge. It has limited size and is useful for batch work only. 24 12  10/12/2024 High Shear granulator (Diosna) 2 Three bladed impellers Chopper 25 High Shear granulator (Diosna) 3 26 13  10/12/2024 High Shear granulator (Diosna) 3 The unmixed dry powders are placed in the bowl and mixed by the rotating impeller for a few minutes. Granulating liquid is then added via a port in the lid of the granulator while the impeller is turning. The granulating fluid is mixed into the powders by the impeller. The chopper is usually switched on when the moist mass is formed, as its function is to break up the wet mass to produce a bed of granular material. 27 Advantages & Disadvantages 3 Advantages: –Fast Granulating step –Simple Process –Good Mixing –Wide Range of Batch Sizes up to 1900 Liters Potential Disadvantages: - Moisture-sensitive products often cannot be processed with aqueous binders. –Requires wet milling, drying and dry milling –Granule size is primarily controlled by milling step 28 14  10/12/2024 Top Drive High Shear Granulator/Mixers Bottom Drive High Shear Granulator/Mixers Mixing Blade or Impeller 29 Collette Gral 3 30 15  10/12/2024 Fluidized bed granulator (FBD) 4 (4X1) The powder particles are fluidized in a stream of air ?????? If the gas is allowed to flow upwards through particles bed at a velocity greater than the setting velocity of the particles, the particles are partially suspended in the gas stream. Heated and filtered air is blown through the bed of unmixed powders to fluidize the particles and mix the powders. Granulation fluid is pumped from a reservoir and sprayed from a nozzle on to the bed of powders. The fluid causes the primary powder particles to adhere when the droplets and powders collide. Escape of material from the granulation chamber is prevented by exhaust filters, which are periodically agitated to reintroduce the collected material into the fluidized bed. The wet granules are then dried in the heated fluidizing air stream. 31 Advantages & Disadvantages 5 Advantages –Relatively Fast Granulation –Good Control of Particle size –Excellent content uniformity –Precise temperature control –Process includes drying step –May not need milling, so total process time and number of process steps can be less than that of a High Shear process –Available in wide range of batch volumes up to 8,400 liters –Multi-functional (drying, granulation, & coating) Disadvantages 1. There is need for relatively high amount of granulating liquid. 2. Fluidized bed granulator is expensive to acquire. 32 16  10/12/2024 Granurex® GXR: Spherical Granulation Starting with a powder blend inside the rotor disc, a binder solution is sprayed onto the powder to form granules The rotor imparts force onto the powder, forming a more spherical granule than with top spray processing Superior Processing Control Independent Control of Airflow and Product Rotation for Precision Granule Sizing and Coating Thickness Complete Processing Flexibility Low Airflow for Coating, Spheronization, Powder Layering and High Density Granulation High Airflow for Drying Product 33 Advantages Relatively Fast Granulation, Spheronization and Powder Layering Produces a Granulation with a very uniform Particle Size, never needs a milling step Process include the drying step Capable of producing a very spherical dense granules Disadvantages More complex process than top Spray Batch sizes are not as large as with other methods, less than 500 Liters depending on the process 34 17  10/12/2024 Increasing Granulation Density Top Spray and Rotor Granulation Density Examples Top-Spray GXR Unprocessed Fluid Bed Tryptophane 0.13 g/cc 0.24 g/cc 0.43 g/cc Sulfamethazine 0.31 g/cc 0.43 g/cc 0.60 g/cc Lactose 0.50 g/cc 0.49 g/cc 0.60 g/cc Ascorbic Acid 0.46 g/cc 0.56 g/cc 0.63 g/cc 35 GXR: Spherical Granulation Why is it done? Creates a very narrow particle size distribution (PSD) Granules are much more spherical than other granulation methods Achieves excellent content uniformity from granule to granule 36 18  10/12/2024 GRANUREX® Case Study: Pellet Generation (Spherical Granulation) Granules produced by the GRANUREX® rotor After 30 minutes of processing within a processor are dense and spherical in shape. The GRANUREX® processor, Ibuprofen pellets were pictures and graphs shown below demonstrate how generated and shown below. Ending product the GRANUREX® rotor processes Ibuprofen from a 7µm poorly flowing powder to 250µm granules with characteristics: 250 micron spherical pellets, 0.59 excellent flow characteristics. g/cc density, with very good flow properties. 37 38 19