FLUIDIZED BED COATING

Abstract

The coating of particulates such as powders, granules, pellets and tablets to produce controlled release dosage forms is becoming increasingly popular. Of the several coating processes available, fluidized bed process is most suitable for the rapid, efficient and reproducible coating of small particles. In particle coating, the degree of agglomeration and spray drying should be minimized in order to produce discrete and well coated particles. A study was therefore conducted to identify and define the important process parameters which governed the success of the coating process. Among the process variables investigated were the fluidizing airflow rate, air temperature, atomizing air pressure, spray angle and spray in interval. The intermittent spray method which allowed partial drying between applications was found to be capable of effectively minimizing undesirable product agglomeration. High process efficiency and uniform coating distribution were achieved with this method. Despite being a prevalent problem in film coating work, only limited study has been carried out on the influence of the inherent tackiness of the coating formulation, a main cause of undesirable substrate agglomeration, on particle coating in a fluidized bed. Towards this end, a simple probe test method which made use of a tensile testing machine, was specially designed to evaluate the tackiness of coating formulations. The tack measurement method was successfully applied to compare the effectiveness of various antitack additives in the coating of lactose granules in the fluidized bed. A mathematical correlation between the tackiness of the coating liquid and the drying time was derived for different methylcellulose (MC)-additive formulations. The correlation provided a valuable basis for predicting processing problems caused by tackiness that may arise when using a given film­ former during the actual coating process. Additives commonly used as antitack agents were found to exert a major impact on the release characteristics of the coated granules. Magnesium stearate, though a highly effective antitack agent, was found to be unsuitable for MC film coatings because of the extreme nature of its release-enhancing action on the polymer film. 'l'he results emphasized the importance of considering the influence of antitack additives on the drug release behaviour of sprayed films formed from water-soluble polymers. The multilayer concept was applied to the design of the drug-coated granules. The multilayer coat on the lactose granules was formed by deposition of methylcellulose of different viscosity grades as drug-containing component layers. The versatility and usefulness of the multilayer concept was aptly revealed in the ability of the drug-coated granules to modify the drug release profiles by the permutation of the component layers as well as the mass ratio of the inner and the outer component layers of the composite coat. The simplicity of the approach arises from the use of just a single type of polymer in the system. The different MC viscosity grades furnish different milieu for drug release control while keeping the chemical nature of the system constant. The multilayer concept for the drug-coated granules was further extended into the development of a gradient layered matrix (GLM) system. In this system, the pattern of drug release can be modified by adjusting the built-in coating composition profile, specifically the drug loading or polymer viscosity across the multilayer coat. The GLM can extend the total duration of release at a relatively low polymer content which is useful in multi-particulate dosage forms particularly for water-soluble systems, which generally require a high coating level for prolonged release. The knowledge gained from this research work provided a basis for more in-depth study of this unique approach of the coating technique to modify the drug release pattern of a completely water-soluble system.

It was also shown that a fast-disintegrating multiple-unit tablet dosage form with satisfactory properties can be readily formulated from these multilayer drug­ coated granules using common pharmaceutical excipients such as microcrystalline cellulose (MCC), crospovidone and colloidal silicon dioxide. The important formulation factors necessary to realize the final solid dosage form were delineated. The good superposition of the cumulative drug release curves of the tablets and their constituent uncompressed coat.ed granules confmned the close simulation of their release profiles.