Evaluation of the Physicochemical Properties of Fine Globular Granules Prepared by a Multi-functional Rotor Processor

Abstract

Multiple regression analysis (MRA) and principal component analysis (PCA) have been used in the present study to examine the relationships between the operational conditions of a unique multi-functional rotor processor, material attributes such as water content during granulation, and a series of associated micromeritics, including the flowability, granule mean size and granule density values. A variety of different operational conditions were tested, including the binder flow rate, atomization pressure, slit air flow rate, rotating speed and temperature of the inlet air. The results of MRA revealed several trends, including (1) the granule mean size was negatively affected by the atomization pressure, and positively affected by the binder flow rate; (2) the granule flow property, Carr's index was positively affected by the atomization pressure, and negatively affected by the slit air flow rate; and (3) the granule density was positively affected by the rotating speed. Taken together, these results suggested that the binder flow rate, atomization pressure and slit airflow rate were critical process parameters for the preparation of fine globular granules. Using PCA, it was possible to examine each relationship of all 19 batches and 10 variables, as well as determine which process parameters or material attributes impacted on the quality of the final product. The PCA results revealed that the roundness was positively correlated with the water content. Therefore, we believe this fundamental information will be important for the development of processes for the facile manufacture of fine globular granules.Key words fine globular granule; flowability; experimental design; multiple regression analysis; multivariate data analysis A large number of functional granules have been developed by the pharmaceutical industry, including granules with sustained release, delayed release, and taste-masking properties. During the coating process in order to add the functionality of granules, if the granules are spheronized, uniform coating of the active ingredient becomes possible, 1) and the solubility behavior can be easily estimated using numerical equations such as Noyes-Whiteny's Equation and Hixson-Crowell's Cube Root Equation.2) The manufacturing processes associated with the preparation of spherical granules are therefore of critical importance.Extrusion-spheronization, centrifugal granulation, and fluidized bed rotogranulation have been applied as manufacturing processes for the preparation of spherical granules. 3-5)Extrusion-spheronization and centrifugal granulation generally require long operation times, and the material handling procedures associated with these processes are considered to be particularly complicated. Fluidized bed rotogranulation frequently leads to particle aggregation, suggesting that the granule mean sizes of the resulting particles are larger than the value required for the desired product. 6)Furthermore, for particles less than 100 µm in size, the application of a uniform film coating process be...

Preparation and Evaluation of Highly Drug-Loaded Fine Globular Granules Using a Multi-functional Rotor Processor

“…Although the rotating speed (X 3 ) had been found to have no effect on the granular roundness during our previous study involving a drug-free formulation, 7) the results of the current study were inconsistent with this finding because the rotating speed was found to have a negative effect on the granule roundness. Furthermore, previous results from the literature revealed similar contradictorily results.…”

“…7) Taken together, these results suggest that the GX system could be used to develop a manufacturing process for the preparation of highly drug-loaded fine globular granules with a particle size of less than 200 µm.…”

“…This result was consistent with that observed for the granular roundness. Furthermore, the results of multivariate data analysis from our previous study using a drug-free formulation revealed that the roundness correlated with the water content in a positive manner, 7) which suggested that the water content of granules could be one of the critical material attributes in terms of its impact on the granular roundness.…”

Preparation and Scale-Up Study of Treated Famotidine for the Development of Orally Disintegrating Tablets Using a Complex Fluidized-Bed Granulator Equipped With a Particle-Sizing Mechanism

“…Before scale-up study on a complex fluidized-bed granulator, the critical process parameter for determining particle size must be known to obtain the desired particle size. Kimura et al reported that the spraying air pressure was identified as one of critical process parameters in granulation process, using a multi-functional rotor processor, Granulex ® [5,6]. We focused on the spraying air pressure as well as the case of using Granulex ® .…”

“…3. One of the problems during preparation of fine particles is the production of largely agglomerated particles [5,6,9] or imperfectly coated particles [9]. It should be noted, however, that in all cases treated FAM had homogenous distributions without largely agglomerated particles or imperfectly uncoated particles.…”