WURSTER COATING- PROCESS AND PRODUCT VARIABLES

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1 WURSTER COATING- PROCESS AND PRODUCT VARIABLES Asija Rajesh *, Dhawan Reetika, Asija Sangeeta, Barupal Ashok Maharishi Arvind Institute of Pharmacy, Jaipur, Rajasthan Abstract In 1959 the wurster process was invented by Dr. Dale Wurster at University of Wisconsin. Because of opportunities in generic business in Indian Pharma Industry almost all major companies are venturing in to particle coating in wurster. The process can be done for both aqueous and non-aqueous applications. The Wurster process provides a high quality reproducible films and highly organised particle flow. This process is capable of handling solvents, suspensions, emulsions, aqueous solutions films and hot melts. It has been used for coating small particles, tablets, pellets, and capsule shell with batch sizes from a few hundred grams up to 600 kg. This process is particularly suitable for a controlled release/ extended release and delayed/ enteric coating of active ingredients layered in the form of pellet. In the Wurster process, a complete sealing of the surface can be achieved. Keywords: Wurster coater (bottom spray coater), process variables, product variables. Introduction The Wurster system combines a coating partition and perforated plate (air distribution plate) to organize the flow of particle. The Wurster machine consists of a cylindrical product container with perforated disc at the bottom. Inside the product container there is second cylinder (coating partition), which is raised slightly above the perforated disk. In the centre of the plate spray nozzle is fitted below the coating partition which is used to dispense the coating solution. The perforated disc is designed with the large hole under the coating partition and one ring at the perimeter, and smaller holes at the remainder of the plate. Due to this design the substrate particles allows to be pneumatically accelerated towards the upward through the coating partition, and downward outside this partition. The particles passing through the coating partition receives a layer of coating material, and dries in the expansion chamber and falls back. During each pass through the coating partition the substrate particles receives an increment of coating material. The particles circulate rapidly in this fashion and cycles are repeated, perhaps several hundred times depending on the coating thickness desired. The quality of film coat applied can be controlled by monitoring key process and product variables [2, 4]. Process variables Batch size: Batch size plays important role in fluidization. At least 50% of volume Corresponding Author Dr. Rajesh Asija 61 P a g e

2 external to coating partition must be occupied by the particles to be coated. This makes it possible to have sufficient quantity of particles inside the partition to accumulate the maximum coating solution droplets and to avoid premature drying, or depositing on the walls of the partition. To calculate load of particles to be introduced following formula can be used- M= (r 1 2 -r 2 2 ) πlρ p Where r 1 and r 2 are chamber radius and partition radius, L is the length of the partition; ρ p is bulk density of particles [7]. Air Distribution Plate: Suitable base plate has to select to get consistent fluidization at minimum attrition. The fluidization volume affects particle velocity; the smaller particle requires lesser air volume to attain certain height than the bigger particles. The differential pressure and air velocity at the air distribution plate must be almost same. Therefore when we deal with the smaller particle we have to use plate with lesser opening area to create the resistance at the Air Distribution Plate to have better distribution of the air [6, 1]. Fluidization Air Flow: The inlet air volume is not to dry the product it has to be used to achieve desired fluidization pattern. The drying of the product can be achieved by adjusting the temperature. For non-aqueous coating a bubbling type of fluidisation in down bed is suggested to minimize the generation of static charge and particle friction, whereas for aqueous coating more rigorous fluidization is needed to have more drying efficiency. At low airflow rates the air passes through the bed without disturbing the solid particles, as air flow is increase some of particles get start to move upward. When the air flow is increase up to certain value particles start moving upward and fell through inner cylinder like a fountain. During this the pressure drop and remain constant, and particle moves in regular way [1, 6, 7]. Fluidization Air Humidity: Inlet air humidity is the most critical factor. It should be considered because before it enters the HEPA filters, get heated and pass through the equipment air is drawn from the external environment. The humidity of air may vary from season to season or day to day. The changes in dew point of air changes the evaporating efficiency of that air.lower humidity in the inlet air will enhance the drying capacity of air even at low temperature but it will cause excessive static charge in the product. To eliminate static charge and process variability, the required specific and absolute level must be set at the initial stage of development itself. Too high absolute humidity will result in a depression in air temperature below dew point, which will cause the condensation of water either on to machine or product substrate surface. It is not recommended to keep high moisture for a highly water soluble substrate at intial stage. The humidity can be increased after the initial coating because the static charge develops only once the pellets are coated with polymers [2, 5,11]. Fluidization Air Temperature: It will depend on the spray rate, type of solvent, tackiness of solution and have direct impact on product humidity and product temperature. For aqueous solvent high temperature is needed to avoid agglomeration of particles while for non- 62 P a g e

3 aqueous solvent low temperature is needed because they get dried at low temperature also. Too high temperature can also cause agglomeration in case of substrate which has tendency to melt or degrade at high temperature. So the temperature is adjusted after considering the various properties of substrate as well as of solvent media. Generally C for organic and C for aqueous solutions are useful at starting for the spray cycle to begin [5, 6]. The bag shaking cycles: The bag shaking cycle should be set as per the conditions present during the process. Larger equipment may have multiple settings for airflow during the dry cycle. Granules are heaviest after the spray cycle and will require maximum fluidization air. As the moisture is driven off, the bed lightens and less fluidizing air is needed to sustain particle flow. Therefore varying levels of air is required throughout. Thus the bag shaking frequency a number of shakings also can vary greatly during the whole process. As the particles become dry and become lighter they tend to migrate into the filter bags increasing the pressure differential. When the pressure exceeds a set point, the bag is shaken. By tracking the time/pressure relationship, it is possible to optimize the bag shaking cycles [8]. Column Height: The height will vary depending on the particle properties shape, flow, size, bulk density and size. The air from the up bed zone must not be diverted towards the down bed, which happens when the column height is too high or batch load is too low. The column must not create a barrier for the particle movement. One has to adjust and keep the column height to get maximum mass flow. During the process frequent change in the column height must be avoided. Even if it is required, it has to be adjusted at a fixed and minimum interval for a process [6, 7, 8]. Spray Rate: In Wurster binary nozzle are used. The droplet formation, spreading, coalescence and evaporation happen almost simultaneously during the process. The spray rate depends on the core particles as well as the solution properties. The evaporation occurs by atomisation air used for the formation of spray mist which results in increase in the droplets viscosity. In case of solvent coating sometime excessive atomisation pressure leads to spray drying portion of spray. The spray rate has to be adjusted according to drying efficiency, tackiness of solution. To coat smaller particles we need to keep the droplet size small either by increasing the atomisation pressure or by decreasing spray rate to avoid agglomeration. At the beginning of coating the spray rate must be kept low to avoid solubilising the core, seepage of the drug or coating polymer in to other layer. Once the initial barrier formed the spray rate can be increased up to the optimum level. It is known that as the particle becomes bigger it can take up more droplets without agglomerating. When the particle enlargement is too high we may require to increase the spray rate in a regular interval [1, 2, 5]. Nozzle and Peristaltic pump: It is difficult to select the proper size tube in the pump. The peristaltic pump generates the pulse. Higher the pump RPM the magnitude of pulse is low. Therefore we have to select smaller internal diameter of tube for the lower spray rate. For the 63 P a g e

4 selection of nozzle, smaller the nozzle insert, more consistent will be spray. However smaller nozzle insert may cause nozzle choking. To avoid agglomeration in wurster coater the coating fluid is to be atomized more finely than in pan coater for tablets. It is necessary that the nozzle used in capable of atomising the coating fluid even if the coating fluid delivery rate is increased. Large droplets of coating fluid generated by low performance nozzle does not distribute evenly over the material to be coated and do not dry quickly as smaller droplets. Very small droplets may dry quickly. Some droplets may contact tablets or beads surface but may dry before getting spread, it will result in to the irregular surface on core material. To maintain uniform atomisation when spray rate exceeds the capacity of nozzle large droplets of coating fluid appears along with small droplets, large droplets results in to the formation of agglomerates. To avoid agglomeration multiple unit nozzles should be used. [1,8, 10,11]. Atomisation Air: If the atomisation pressure is high then the mist size will be lower, then the chances of agglomeration will also low. Excess pressure will lead to a particle shooting to the filter bag. The atomisation pressure varies from 2 bar to 4 bar. This will depend upon the kind of binder used its evaporation rate and its viscosity. If in the finished granulation lumps of binder is present, then that would mean the air pressure has been lower than required. The atomisation air must be adjusted to keep enough to avoid agglomeration. During the optimisation of spray rate to achieve fastest possible process, one has to keep droplet very small. Higher the pressure smaller will be droplet [2, 5, 7]. Product variables Core particle: In some cases the core particles are used, it can be drug core itself like spherodised and extruded product or pellets of inert material used to load drug. Controlled release of drug is mainly dependent upon the thickness of the film on the pellets. If the specifications set for the core is not rigid enough and if the average particle size of core varies, even by 50 micron, this will lead to considerable change in the film thickness with same % coating. Particle surface: If the particle surface will rough the total coating area available for coating will change. The pellets with rough surface will have more surface area then a pellet with smooth surface. To cover edges and crevices of rough pellets one has to make film thicker but the total quantity applied typically may exceeds the minimum required for acceptable performance. And large pores may never be covered, resulting in an imperfection in the film. Due to attrition during the process it is not easy to preserve the drug pellets as smooth as possible. In one instance, the product temperature in drug loading stage changed.when the product temperature reduced from 60 to 35 C, on the whole SR coating required to get desired release was diminished from 21% to 12% even though all parameters in SR coating kept same. This is mainly due to smooth surface of the drug pellets when processed at low temperature due to reduced spray drying and higher moisture. When the drug loading was done at higher temperature, the surface of drug loaded 64 P a g e

5 pellets was rough and porous due to spray drying effect. To cover these pores one has to apply more coating. Particle size: As the particle size decreases the amount of coating material require for desire thickness becomes very high. The quantity of liquid also increases as a result of decrease in particle size because coating substance must be applied using some medium which is solid concentrations in liquid in range of 10 to 30%. Further complication is that as the particle size decreases agglomeration becomes more dependent on the formulation of the coating liquid and nozzle which is unavoidable. So it suggested to use large particle size that may reasonably produce the desired results [6]. Product temperature: Specification of product temperature will depend upon the glass transition temperature of polymer. To get maximum efficiency it is we have to keep product temperature as low as possible. Lower the product temperature lesser will be the static charge generation but for some polymer like HPMC we have to maintain high temperature to minimise the agglomeration by drying the film effectively [1, 7]. Solution Viscosity and Solution Concentration: We have to optimise these parameters to have better control on the process. We have to reduce the spray rate if the solution is viscous and tacky. It is generally known that, higher solid content will reduce the process time. But it is opposite in case of polymers like HPMC and ethyl cellulose when they are in solution form. As we increase the solid content beyond certain limit for these polymers, the spray rate will reduce radically, which results in higher process time [2, 6]. Bulk Density of Finished Product: Once it was thought it is uncontrollable property but research has shown that by concentrating on two variables it can be reduced or altered. These factors are the in process moisture and the fluidizing air volume. The lowest possible finished product bulk density can be achieved by keeping the bed moisture at or below the maximum finished product moisture during spraying. In this way drying stage (which can cause product attrition and increased bulk density) is not needed after spraying. Volume of fluidizing air can be affected by several factors. As the outer air filter or the product bowl screen becomes occluded by binder, by coating material, or by fine powders resistance to air flow increases. Without a warning indicator the volume of air can drop enough to cause the bed moisture to increase therefore increasing the bulk density of finished product [1, 6]. References 1. Jones David M. Factors to Consider in Fluid Bed Processing. Pharmaceutical Technology.April Dr. Mehta Atul M. Scale up Considerations in the Fluid Bed Process for Controlled Release Product. Pharmaceutical Technology. Feb Lachman Leon, Lieberman Herbert A. Kanig Joseph L.The Theory and Practice of Industrial Pharmacy. 3rd ed. Bombay: Varghese publishing house.1987: P a g e

6 4. Swarbrick J, Boylan J.C. Encyclopaedia of Pharmaceutical Technology. vol1. New York: Marcel Dekker INC. 1992: Swarbrick J, Boylan J.C. Encyclopaedia of Pharmaceutical Technology.vol 6. New York: Marcel Dekker INC.1992: Shetty Vasant. Wurster Coating - Scale up and Scale out. Pharma times. November 2010;42 (11): Mafadi EL S, Hayert M, Poncelet D. Fluidization control in the wurster coating process. Chem.Ind.2003; 57(12): /fbp1.pdf. 9. Chauhan Jitender, Yadav Poonam.Study of scale up parameters of fluidized bed coating. Der Pharmacia Sinica Availablefrom:URL: rchlibrary.com/der-pharmacia- sinica/vol2-iss1/dps pdf. 10. Harlan S Hall. Scaling of fluid bed coating. Pharmatech.2004; McGinity James W., Mehta Ketan A., Frisbee Steven E. Processing factors that influence the in vitro in vivo performance of film coated drug delivery system. Drug Development and Delivery.2002; 2(1). 66 P a g e