RESUMEN
INTRODUCTION: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration brought about by the spray addition of the binding liquid onto a stationary bed of powder particles that is transformed to a fluid-like state by the passage of air through it. AREAS COVERED: The basic working principles, equipment set-up, advantages and challenges of fluidized bed granulation are introduced in this review. This is followed by an overview of the formulation and process-related variables affecting granulation performance. Technological advances, particularly in the application of process analytical tools, in the field of fluidized bed granulation research are also discussed. EXPERT OPINION: Fluidized bed granulation is a popular technique for pharmaceutical production, as it is a highly economical and efficient one-pot process. The research and development of process analytical technologies (PAT) has allowed greater process understanding and control to be achieved, even for the lesser known fluidized bed techniques, such as bottom spray and fluidized hot melt granulation. In view of its consistent mixing, as well as continuous and concurrent wetting and drying occurring throughout processing, fluidized bed granulation shows great potential for continuous production although more research is required to fully implement, validate and integrate the PAT tools in a production line.
Asunto(s)
Polvos , Tecnología Farmacéutica/métodos , Tecnología Farmacéutica/instrumentaciónRESUMEN
The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.
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Composición de Medicamentos/instrumentación , Composición de Medicamentos/métodos , Tecnología Farmacéutica/métodos , Formas de Dosificación , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polvos/análisisRESUMEN
BACKGROUND: Growing interest in the use of the less-explored bottom spray technique for fluidized bed granulation provided impetus for this study. AIM: The impact of fluid dynamics (air accelerator insert diameter; partition gap) and wetting (binder spray rate) on granule properties were investigated. METHOD: In this 3(3) full factorial study, the results were fitted to a quadratic model using response surface methodology. The air velocity at the spray granulation zone for the investigated conditions was measured using a pitot tube. RESULTS: Air accelerator insert diameter correlated to measured air velocity at the spray granulation zone and was found to not only dictate growth but also influence granule morphology. The partition gap was found to play important roles in regulating particle movement into the spray granulation zone and optimizing process yields, whereas binder spray rate significantly affected granule morphology but not granule size. CONCLUSIONS: Unlike conventional fluidized bed granulation, ease of modulation of fluid dynamics and insensitivity of the bottom spray process to wetting allow flexible control of granule size, shape, and flow. Its good drying ability also indicated potential use in granulating moisture-sensitive materials.
Asunto(s)
Química Farmacéutica/métodos , Preparaciones Farmacéuticas/síntesis química , Tamaño de la Partícula , Preparaciones Farmacéuticas/metabolismo , Distribución Aleatoria , ReologíaRESUMEN
The aim of this study was to investigate the nature of Supercell coating, an on-line tablet coater that employed a unique pattern of airflow. Tablets coated at different spray rates (4, 6, 8, 10, and 12 mL/min) were analyzed to investigate the influence of different wetting conditions on the quality of coats formed. Scanning electron micrographs showed that tablet coats formed at a spray rate of 4 mL/min consisted of spray-dried droplets that did not coalesce. At a spray rate of 6 mL/min, surface roughness was found to be lower than at the other spray rates, and the coat appeared smoothest, whereby droplets seemed fused together. At higher spray rates, the droplets appeared as branching arms and scale-like structures. This was attributed to the spread of spray droplets by the processing air and mass transfer of wet coating materials between tablets. Further tests showed that coats formed at higher spray rates had higher drug yield, drug uniformity, color uniformity, and density. However, the variability in coat thickness was increased due to the mass transfer of coats and dissolution of tablet core surfaces by the coating material. Since coats of different characteristics can be formed in Supercell coating, the choice of wetting conditions would depend on the type of coat required and the coating materials used.