Application of Fluidized Hot-Melt Granulation (FHMG) for the Preparation of Granules for Tableting; Properties of Granules and Tablets Prepared by FHMG

ABSTRACT The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.

[1]  L. Yang,et al.  Characterization of compressibility and compactibility of poly(ethylene oxide) polymers for modified release application by compaction simulator. , 1996, Journal of pharmaceutical sciences.

[2]  H. Sakamoto,et al.  Study of standard tablet formulation based on fluidized-bed granulation. , 1998, Drug development and industrial pharmacy.

[3]  H. Larhrib,et al.  Compression of thermally treated Polyethylene glycol 10,000 , 1997 .

[4]  Masao Kobayashi,et al.  Application of Tumbling Melt Granulation (TMG) Method for Controlled Enteric-Release Beads by Coating Mixture of Hydrogenated Castoer Oil and Higher Fatty Acid , 1997 .

[5]  Torben Schæfer,et al.  Melt pelletization in a high shear mixer. I: Effects of process variable and binder , 1992 .

[6]  Masao Kobayashi,et al.  Application of Tumbling Melt Granulation (TMG) Method for Preparing Controlled Release Beads Coated with Hydrogenated Castor Oil , 1997 .

[7]  Masao Kobayashi,et al.  Preparation of Spherical Beads without Any Use of Solvents by a Novel Tumbling Melt Granulation (TMG) Method , 1997 .

[8]  J. R. Partington,et al.  The properties of solids , 1952 .

[9]  H. Kristensen,et al.  Melt pelletization in a high shear mixer. IV. Effects of process variables in a laboratory scale mixer , 1993 .

[10]  R L Carr,et al.  EVALUATING FLOW PROPERTIES OF SOLIDS , 1965 .

[11]  Torben Schæfer,et al.  Melt pelletization in a high shear mixer. VIII. Effects of binder viscosity , 1996 .

[12]  H. Lieberman,et al.  Pharmaceutical dosage forms : tablets , 1980 .

[13]  T. Murakami,et al.  Preparation of Essential Oils Loaded Granule by Melt Granulation , 1994 .

[14]  H. Kristensen,et al.  Melt pelletization in a high shear mixer. III: Effects of lactose quality , 1992 .

[15]  R L Carr,et al.  CLASSIFYING FLOW PROPERTIES OF SOLIDS , 1965 .

[16]  Torben Schæfer,et al.  Melt pelletization in a high shear mixer. IX. Effects of binder particle size , 1996 .