Impact of Spray Location on Coated Granule Quality Using Fluidized Bed Coating - Essay Example

Impact of Spray Location on Coated Granule Quality Using Fluidized Bed Coating Introduction: granule coating and fluidized bed coating Granule coating is a widespread and essential technique in the pharmaceutical and food industries. Basically, it involves the application of a film or coating to small solid particles, or fluid droplets for various aesthetic and protective purposes.(Teunou and Poncelet) This goal may be achieved by a number of technological processes including solvent extraction, coacervation, extrusion, spray drying, rotating drum coating, or fluidized bed coating, which is the focus of this review. Fluidized bed coating has been recognized as the best method for granule coating.(Teunou and Poncelet) It produces a kind of coating around reservoir-system microcapsules which could be single-layered or multi-layered. The fluid bed works on the principle of maintaining small solid particles in a suspended state within a confined space by channeling a gas stream through the powder bed. It is used for several purposes including granulation, coating, drying, and pelletization.(Teunou and Poncelet; Yang et al.; Olsen "Batch Fluid-Bed Processing Equipment - a Design Overview: Part I,") In the food industry, fluidization is used in freezing and cooling, freeze drying, puffing, classification, blanching, and cooking.(Dewettinck and Huyghebaert) Essentially, fluidized bed coating entails the introduction of granules into a coating cell and fluidization by air flow. The coating substance is sprayed through a nozzle with the aim of achieving a homogenous layering of the coating material on the granule. The process may be done as a batch or continuous one. Current industry trends favor the use of the continuous process over the batch process, in order to optimize efficiency of operation, and consistency of product quality.(Teunou and Poncelet) Applications in food, cosmetic, and pharmaceutical industry In the food industry, granule coating can be used to prepare encapsulated powders which separate reactive components in a mixture, mask unpleasant taste or flavor, protect unstable ingredients from degradation by environmental factors, reduce hygroscopicity, or provide controlled release.(Teunou and Poncelet) It also produces modified flow, compression, dust reduction and density properties in the coated products.(Teunou and Poncelet) The method has been used to encapsulate enzymes, labile proteins, yeast and aromas in polysaccharide matrices and for film coating of extruded products by lipids, resins, or proteins.(Teunou and Poncelet) Maa et al. reported the coating of lactose granules with recombinant human deoxyribonuclease using spray coating technologies.(Maa, Nguyen and Hsu) In food processing, The applications of fluidized bed coating in the food industry have been reviewed by a number of authors.(Dziezak; Arshady; Duxbury and Swientek) A recent review by Werner et al. looked at the current state of the art with respect to air-suspension particle coating in the food industry.(Werner et al.) In the pharmaceutical industry, fluidized bed coating is utilized in the facilitation of delayed, sustained or controlled release; selective enteric release, masking of taste, stability to degradation, and pharmaceutical elegance.(Dewettinck and Huyghebaert) Explanation of different spray location technologies There are three classic geometries for spray coating location: the top spray, bottom spray (or "wurster" spray), and tangential (or side) spray with rotating disk(Olsen "Batch Fluid-Bed Processing Equipment - a Design Overview Part 2"; Yang et al.). Top-spray Method The oldest spray location technology is the top spray method, in which the spray nozzle is located atop the fluid bed chamber, and the sprayed droplets move countercurrently to the air flow.(Yang et al.) It was developed from the older fluidized bed dryers.(Dewettinck and Huyghebaert) It involves the acceleration of granules from a container past a nozzle which sprays the coating countercurrently on the fluidized particles.(Dewettinck and Huyghebaert) The coated granules then move into an expansion chamber, from where they fall back into the product container to continue the process in a cycle again.(Jones) The method has been successfully used for materials as small as 100 microns.(Jones) The steady-state thermodynamic operation point of top-spray fluidized bed processing has been studied by Dewettinck using a modeling technique.(Dewettinck et al.) Figure 1: Top-spray fluidized bed coating schematic (adapted from Dewettinck et al.(Dewettinck and Huyghebaert)) Bottom Spray Method The bottom spray fluidized bed coater sprays the granules from the bottom, as the name implies. The liquid spray is done concurrently with the fluidizing air flow.(Yang et al.) A modification of the system (the Wurster chamber), features continuous circulation of the particles in a sort of spouted bed construction, which increases the drying rate. Products thus formed possess better homogeneity in the coating, which is suitable for controlled release capsules and variable-sized particles. Figure 2: Bottom spray fluidized bed coating schematic (adapted from Dewettinck et al.(Dewettinck and Huyghebaert)) Rotating disk with Tangential Spray Method The rotor disk with side spray system employs a rotating disk inside the fluidizing cell. The spray gun on the chamber's side sprays the coating at a tangent to the direction of rotation. The combination of centrifugal, gravitational, and vertical forces enhance the efficiency of the system.(Yang et al.) Figure 3: Tangential spray fluidized bed coating schematic (adapted from Dewettinck et al.(Dewettinck and Huyghebaert)) Comparison of spray location technologies with respect to granule quality The mode of spray used in coating granules determines the spray pattern of the coating, as well as the manner in which the coating impinges and spreads on the granules. Therefore, it is an important determinant of film coating structure and ultimately, coated granule quality.(Mehta and Jones) This dependency has been reported for a number of enteric coated granules.(Mehta) The Wurster spray system has been described as the most adequate for particle coating, although it is beset by the disadvantage of high cost, which is a disadvantage in the food industry.(Teunou and Poncelet) The bottom spray approach ensures a higher degree of interaction between coating and granules and results in better coating efficiency. Also spray droplet drying is reduced; hence the production of fines is minimized.(Teunou and Poncelet) Because the droplet path is short, premature evaporation hardly occurs, droplet viscosity is minimal, and a dense film with excellent physical properties can be formed.(Dewettinck and Huyghebaert) However, it has been reported that coated film thickness varied with particle size for bottom-spray coated granules.(Wesdyk et al.) The top spray method has been shown to be inefficient in terms of deposited material and coating quality, because spray drying of droplets led to production of unwanted fine particles, thus diminishing the controlled release kinetics of final capsules. However, it has advantages in terms of accessibility and capacity. With the rotating disk system, due to the simultaneous rotation and air flow, the coated granules possess a higher density and spherical shape, with a quality comparable to the Wurster system. However, because there is considerable agitation, it is not useful for coating granules with a high degree of friability.(Yang et al.) In a study of the effect of spray mode of fluid-bed coating equipment and other parameters on an aqueous-based ethylcellulose coating for propranolol hydrochloride pellets,(Yang et al.) it was reported that bottom-spray coated pellets released the drug at a slower rate than the top-spray coated pellets. This difference was attributed to the physical properties and deposition of the spray droplets, which presumably impacted on the film structure.(Yang et al.) The top-spray coated pellets released the drug faster because of inadequate coating of the particle surface, variable coating thickness, and compromised film integrity, which result from irregular motion of the particles in the fluidizing chamber due to the countercurrent air flow. It is also known that spray drying may occur from the before the spray liquid comes in contact with the particle, due to the nature of the air flow. Evaluation of the coated pellets by scanning electron microscopy (SEM) revealed a rough and flaky appearance of top-spray coated pellets as opposed to the smooth and even surface of bottom-coated pellets. However, because the chamber geometry in some of the experiments were not uniform, it is possible that the differences in film quality may not be due to the spray mode alone. The top-spray configuration does not allow for controlling the distance the droplets travel before coating, leading to premature evaporation and compromised coating quality.(Jones) In the food processing industry, it does appear that the top-spray coating method holds the greatest promise of widespread use because of its greater capacity per batch, versatility, and simplicity of machinery/operation.(Dewettinck and Huyghebaert) Wesdyk et al.(Wesdyk et al.) investigated the effect of spray mode and process parameters on the variation in coated film thickness in a bead formulation, for a fixed particle size range and distribution. Because of the postulated premise that the variation of film thickness depended on differences in fluidization patterns and velocities of the various size granules, it seemed reasonable that the mode of spray coating, among other process parameters, may affect the degree to which changes in fluidization pattern occur. The coated beads were evaluated on the basis of tests of bulk density, dissolution rate, scanning electron microscopy, and coating efficiency. Their results showed that the coated granules prepared by the bottom spray process had a film thickness variation which correlated with bead size, whereas the top and tangential spray mode products showed no consistent dependency of film thickness on bead size. Besides, the top spray coated beads were also believed to have suffered from solubilization of core components into the film. These results were confirmed by dissolution testing data, which showed that in bottom spray coated beads, the surface-area-normalized release rates varied with the size of the bead, whereas the top-spray or tangential-spray coated beads showed a normalized release rate that was independent of bead size. These results were explained as to being related to the design of the different spray modes. In the top spray design, the randomization caused by bubbling or spouting in the fluidized bed restricts the possibility for segregation or variations in bead velocity that could facilitate consistent film thickness variability. Similarly, in the tangential spray mode design, there is a low potential for particle-size-based segregation due to the combination of fluidizing air, centrifugal, and gravitational forces which lead to a restrictive helical fluidization. In contrast however, segregation of particles occurs as they exit the Wurster column and decelerate in the expansion chamber and the variable particle velocities as they went through the coating zone. The authors noted in conclusion that other advantages and disadvantages were associated with each spray mode, in addition to film thickness variation. These include poor quality of films formed using top spray coating and product attrition due to shear effects in the rotary side-spray system.(Mehta and Jones) Techniques for assessing coated granule quality There are several experimental techniques available for the characterization of granules, by which the comparative quality of coated granules may be assessed. These techniques have been extensively reviewed by Sinko.(Sinko) Basically, they consist of the following approaches: Particle morphology This may be characterized either by optical microscopy or scanning electron microscopy, the latter offering a superior resolution, sensitivity, and wealth of information on the topology of the surface coating. The shape of the granule is studied by quantitative models.(Sinko) Particle size analysis This is done to assess the variation or uniformity of the particle size distribution. Techniques employed include optical microscopy, sieve analysis, or laser light analysis. The preferred methods are dry sieve analysis and microscopy, as opposed to light scattering, due to the relatively large size of granules.(Sinko) Of these methods, microscopic measurements offer the greatest potential for accuracy, although it is the most arduous in terms of physical strain. Software-based analysis of the image can greatly speed up the data processing, although this may be confounded by three-dimensional surface effects. The dry sieve analytical method is simple but gives only rudimentary information. The results are obtained in terms of percentage retained on the sieve, or percentage of oversized or undersized particles. Dissolution testing This is performed to determine the time course (kinetics )of dissolution of the granules, and it provides a surrogate means of assessing the eventual in vivo performance of the final product. Flow properties and density Because in certain cases coating is done in order to modify flow properties, measurements of flowability and bulk density could be useful in assessing the suitability of coated granules. Granule Strength Measurements of granule strength may be done in combination with dissolution testing in order to predict the friability and disintegration characteristics of coated granules. A novel method of assessing core granule friability in coated granules in which the granules were subjected to a strong impact was recently reported by some workers.(Hamashita et al.) Thermal analysis This involves the use of differential scanning calorimetry and thermogravimetric analysis to assess the chemical composition of the coated granules. Because the coating material is essentially different than the core, it allows one to analyze the composition by mass of coating versus core chemicals. Conclusion This review has examined the current literature covering the impact of spray location on the quality of coated granules. The applications of spray coating in the pharmaceutical and food industries were looked into, as well as the different geometries of operation of spray coating chambers. The comparative evaluation of these different approaches to spray coating was done with respect to effects on the final quality of coated granules in terms of coating uniformity, coating thickness, and potential for attrition and production of fines. Finally, a brief overview of available methods for characterizing coated granules was provided. WORKS CITED Arshady, R. "Microcapsules for Food." Journal of Microencapsulation 10 (1993): 413-35. Dewettinck, K., and A. Huyghebaert. "Fluidized Bed Coating in Food Technology." Trends in Food Science & Technology 10.4-5 (1999): 163-68. Dewettinck, Koen, et al. "Modeling the Steady-State Thermodynamic Operation Point of Top-Spray Fluidized Bed Processing." Journal of Food Engineering 39.2 (1999): 131-43. Duxbury, D. D., and R Swientek, J. "Encapsulated Ingredients Face Healthy Future." Food Processing 53 (1992): 38-46. Dziezak, J. D. "Microencapsulation and Encapsulated Ingredients." Food Technology 42 (1988): 136-53. Hamashita, T., et al. "Granulation of Core Particles Suitable for Film Coating by Agitation Fluidized Bed I. Optimum Formulation for Core Particles and Development of a Novel Friability Test Method." Chemical & Pharmaceutical Bulletin 55.8 (2007): 1169-74. Jones, D. M. "Controlling Particle Size and Release Properties." Flavor Encapsulation. Eds. S.J. Risch and G.A. Reineccius. Washington DC: American Chemical Society, 1988. 158-75. Maa, Y. F., P. A. Nguyen, and C. C. Hsu. "Spray-Coating of Rhdnase on Lactose: Effect of System Design, Operational Parameters and Protein Formulation." International Journal of Pharmaceutics 144.1 (1996): 47-59. Mehta, A. M. "Evaluation of Fluid Bed Processes for Enteric Coating Systems." Pharmaceutical Technology 10 (1986): 46-56. Mehta, A. M., and D. M. Jones. "Coated Pellets under the Microscope." Pharmaceutical Technology 9 (1985): 52-60. Olsen, K.W. "Batch Fluid-Bed Processing Equipment - a Design Overview Part 2." Pharmaceutical Technology 13.6 (1989): 39-50. ---. "Batch Fluid-Bed Processing Equipment - a Design Overview: Part I,." Pharmaceutical Technology 13 (1989): 34-46. Sinko, Christopher. "Granulation Characterization: Methods and Significance." Handbook of Pharmaceutical Granulation Technology. Ed. Dilip Parikh. New York: Marcel Dekker, 1997. 419-70. Teunou, E., and D. Poncelet. "Batch and Continuous Fluid Bed Coating - Review and State of the Art." Journal of Food Engineering 53.4 (2002): 325-40. Werner, Stephen R. L., et al. "Air-Suspension Particle Coating in the Food Industry: Part I -- State of the Art." Powder Technology 171.1 (2007): 25-33. Wesdyk, R., et al. "Factors Affecting Differences in Film Thickness of Beads Coated in Fluidized Bed Units." International Journal of Pharmaceutics 93.1-3 (1993): 101-09. Yang, Shirley T., et al. "The Effect of Spray Mode and Chamber Geometry of Fluid-Bed Coating Equipment and Other Parameters on an Aqueous-Based Ethylcellulose Coating." International Journal of Pharmaceutics 86.2-3 (1992): 247-57. Read More