FLUIDIZED BED GRANULATION AND POLYMERIC COATING OF PARTICLES

Abstract

This study involves the aspects of both granulation and coating of particles as a one-pot-process in fluidized bed equipment. Granulation to produce core granules was carried out with different process and product variables. Generally, an increase in the concentration, spraying rate and volume of binder solution caused an increase in granule size and a narrower particle size distribution which then affected the poured and tapped densities of the granules. Granules prepared using polyvinylpyrrolidone (PVP) K90 solution grew by aggregate agglomeration. Granules prepared using PVP K120 solution were formed through snowballing as the primary agglomeration process. This occurred at low binder solution concentration with aggregate agglomeration taking place when the binder solution concentration was increased. Material such as drug dissolved in binder solution influenced the rheological properties of the resultant solution formed. Binder solution containing dissolved material did not impart the same granule characteristics, particularly granule size and shape, as that of binder solution without other dissolved material. The choice of an appropriate binder solution and process conditions was important for successful production of granules without the catastrophic effects of both dry and wet quenching. The mode by which a drug is incorporated into granules governs the uniformity of drug distribution across the different sizes of fluidized bed granules. Drug dissolved in PVP solution appeared to be the best method of drug incorporation. It provided a means of easy drug delivery to the powder load during fluidized bed processes. Coating of core granules with acrylic polymer dispersions and hydroxypropylmethylcellulose (HPMC) solutions were carried out consecutive to the granulation process in the fluidized bed equipment which generated the core granules required for coating. The size and mechanical strength of core granules were important considerations in the choice of granules suitable for coating. Cores of higher crushing strength values when coated gave longer dissolution t50% values. The drug release could be further modified by varying the coating level, adding additives such as fatty acid and sodium salt of fatty acid or compressing the coated granules into tablets. The increase in the coating level can be achieved by adding talc to the coating solution. However, the presence of talc or sodium oleate affected the bonding of granules in the tablet and thus the crushing strength of tablets. HPMC with sodium salt of fatty acid coat provided on hydration in the dissolution medium, a gel barrier, which can help to retard the drug release. When the amount of talc and sodium oleate present in the coat of granules used for tableting was high, the drug release rate was increased despite the increase in the coating level of HPMC. Thus, coating solution formulation affected the property of coated granules and the resultant compressed tablets.