A novel insight into fluid bed melt granulation: Temperature mapping for the determination of granule formation with the in-situ and spray-on techniques

Abstract

The in-line control of pharmaceutical processes has become a necessary tool for the evaluation and follow-up of pharmaceutical dosage forms. In this study, a novel approach to the evaluation of conditions established in a conical fluid bed granulator during the in-situ and spray-on fluid bed melt granulation (FBMG) techniques was developed. The determination of temperature mappings allowed the characterization of the critical zones during the melt granulation and the prediction of the volume of the wetting zone, hence enabling the identification of the areas of optimal granule growth. Two grades of polyethylene glycol (PEG 2000 and 6000) were used as meltable binders in three binder spraying rates and droplet size fractions for spray-on and three binder particle sizes and contents for in-situ. The results showed the presence of intense heat exchange in the bottom of the bed during the in-situ technique and under the spraying nozzle during the spray-on technique, identified as the wetting zone. Isotherm maps enabled the identification of the transition between the wetting, cooling and consolidation zones for the spray-on and the cooling zone for the in-situ technique. The shape and volume of the wetting zone was highly dependent on binder spraying rate and spraying pressure for spray-on and binder particle size and content for in-situ FBMG. Granule size and size distribution were correlated to the volume of the wetting zone and an optimized wetting volume interval was determined for both spray-on and in-situ techniques for the optimal quality attributes of the granules.

Keywords: Granule size distribution; Image analysis; In-line temperature acquisition; Isotherm maps; Spray-on and in-situ FBMG; Volume of wetting zone.