Compression characteristics of granulated materials. IV. The effect of granule porosity on the fragmentation propensity and the compatibility of some granulations

Abstract Eleven granulations of a common filler (lactose) and three granulations of a high dosage drug (dipentum) were produced by wet granulation with polyvinylpyrrolidone as binder in a high shear mixer. The agglomeration process was varied to produce granulations with varying granule porosity. The size fraction 500–710 μm was separated and characterised on binder content (lactose granulations), granule porosity and friability. The granule fragmentation during compaction was evaluated by measurements of the air permeability of the tablets. Finally, the diametral compression strength of tablets compacted from unlubricated granulations and lactose granulations lubricated with 0.5% by weight magnesium stearate at 150 MPa was measured. The results showed that the degree of granule fragmentation during compaction was related to the granule porosity before compaction. A granulation with a higher porosity had a higher fragmentation propensity, as evaluated by the permeametry measurements, and the tablet strength was less affected by magnesium stearate addition. The tablet strength correlated well with the degree of fragmentation, i.e. a granulation with higher degree of fragmentation gave tablets of a higher mechanical strength. These observations suggest that variations in compactibility, when the same formulation is wet granulated under different process conditions, can be explained by variations in granule porosity.

[1]  R. C. Rowe,et al.  Surface free energy and polarity effects in the granulation of a model system , 1989 .

[2]  A. B. Selkirk,et al.  An investigation of the pore structure of tablets of sucrose and lactose by mercury porosimetry , 1970, The Journal of pharmacy and pharmacology.

[3]  G. Alderborn,et al.  Studies on direct compression of tablets X. Measurement of tablet surface area by permeametry , 1985 .

[4]  D Ganderton,et al.  A comparison of granules prepared by pan granulation and by massing and screening , 1971, The Journal of pharmacy and pharmacology.

[5]  R. Haines‐Nutt,et al.  Elastic recovery and surface area changes in compacted powder systems. , 1972, The Journal of pharmacy and pharmacology.

[6]  G. Alderborn,et al.  Compression characteristics of granulated materials. I. Fragmentation propensity and compactibility of some granulations of a high dosage drug , 1987 .

[7]  M. Adams,et al.  A fracture mechanics approach to the breakage of particle agglomerates , 1987 .

[8]  P. Holm,et al.  Effect of Impeller and Chopper Design on Granulation in a High Speed Mixer , 1987 .

[9]  H. Kristensen,et al.  Granulation in high speed mixers. III: Effects of process variables on the intragranular porosity , 1984 .

[10]  G. Bolhuis,et al.  Magnesium stearate susceptibility of directly compressible materials as an indication of fragmentation properties , 1988 .

[11]  A. B. Selkirk,et al.  The effect of granule properties on the pore structure of tablets of sucrose and lactose , 1970, The Journal of pharmacy and pharmacology.

[12]  G. Alderborn,et al.  Compression characteristics of granulated materials. III, The relationship between air permeability and mechanical strength of tablets of some lactose granulations , 1990 .

[13]  R. Rowe.  Polar/non-polar interactions in the granulation of organic substrates with polymer binding agents , 1989 .

[14]  D. Cheng,et al.  The tensile strengths of single powders and binary mixtures , 1983 .

[15]  R. Rowe.  Binder-substrate interactions in tablets: a theoretical approach based on solubility parameters , 1988 .

[16]  G. Bolhuis,et al.  BONDING CHARACTERISTICS BY SCANNING ELECTRON-MICROSCOPY OF POWDERS MIXED WITH MAGNESIUM STEARATE , 1978 .

[17]  C. Nyström,et al.  Studies on direct compression of tablets. VI. Evaluation of methods for the estimation of particle fragmentation during compaction. , 1982, Acta pharmaceutica Suecica.

[18]  J. Schwartz,et al.  The Strength of Microcrystalline Cellulose Pellets: The Effect of Granulating with Water/Ethanol Mixtures , 1990 .

[19]  J. Fell,et al.  Granulation and compaction of a model system. I: Granule properties , 1986 .

[20]  A. B. Selkirk,et al.  The influence of wet and dry granulation methods on the pore structure of lactose tablets , 1970, The Journal of pharmacy and pharmacology.

[21]  J. van der Zwan,et al.  The compaction and mechanical properties of agglomerated materials , 1982 .

[22]  M. Ritala,et al.  Influence of Liquid Bonding Strength on Power Consumption During Granulation in a High Shear Mixer , 1988 .

[23]  J. Newton,et al.  Determination of tablet strength by the diametral-compression test. , 1970, Journal of pharmaceutical sciences.

[24]  D. Ganderton,et al.  The effect of particle size on the granulation of lactose by massing and screening. , 1972, The Journal of pharmacy and pharmacology.

[25]  D. Ganderton,et al.  The influence on pharmaceutical granulation of the type and capacity of mixers. , 1973, The Journal of pharmacy and pharmacology.

[26]  Torben Schæfer,et al.  Granulation in different types of high speed mixers. I: Effects of process variables and up-scaling , 1986 .

[27]  G. Alderborn,et al.  Compression characteristics of granulated materials. II, Evaluation of granule fragmentation during compression by tablet permeability and porosity measurements , 1990 .