Compression characteristics of granulated materials: VI. Pore size distributions, assessed by mercury penetration, of compacts of two lactose granulations with different fragmentation propensities

Wikberg, Martin; Alderborn, Göran

doi:10.1016/0378-5173(92)90059-b

Cited by 38 publications

(8 citation statements)

References 10 publications

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“…This is consistent with the finding by Wikberg and Alderborn that demonstrated wider and bimodal pore size distribution for the tablets compressed from granulation with low porosity compared to the narrower and smaller pore size distribution for tablets compressed from the more porous granulation [7]. Porosity of DPC 963 tablets compressed using similar compression force and manufactured using drug substance lots with different particle sizes.…”

Section: Granulation Porositysupporting

confidence: 91%

Effect of drug substance particle size on the characteristics of granulation manufactured in a high-shear mixer

2000

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DPC 963 is a non-nucleoside reverse transcriptase inhibitor with low aqueous solubility. The effect of DPC 963 drug substance particle size on the characteristics of granules manufactured by high-shear wet granulation was evaluated. The wet granulation process was used to manufacture a DPC 963 formulation with high drug loading. The formulation was manufactured using drug substance lots with different particle size distributions. Granulation particle size distribution, porosity, and compressibility were determined. A uniaxial compression test was also performed on moist compacts of the formulation prepared with different particle size distributions. Particle agglomeration behavior was affected by drug substance particle size. Granulation geometric mean diameter and fraction with particle size greater than 250 µm was inversely proportional to the drug substance particle size. Mercury intrusion porosimetry revealed higher pore volumes for the granules manufactured using the drug substance with the smaller particle size, suggesting lower tendency for granule densification than for that manufactured with the larger drug substance particle size. Granulation compressibility was also sensitive to changes in drug substance particle size. A decreased drug substance particle size led to increased granulation compressibility. Results from the uniaxial compression experiments suggested that the effect of particle size on granulation growth is the result of increased densification propensity, which in turn results from increased drug substance particle size.

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Section: Granulation Porositysupporting

confidence: 91%

Effect of drug substance particle size on the characteristics of granulation manufactured in a high-shear mixer

2000

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“…Note that typically lactose is compacted at 2-15 kN. 47 The particle densities (D D ) are calculated using the helium pycnometry technique, then using porosity = (1−D b /D D ), it is possible to calculate the porosity of the powder compacts. Table 1 lists the particle densities, bulk densities, and the porosities calculated using the above equation.…”

Section: Microstructure Analysismentioning

confidence: 99%

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

Yassin

Lin

et al. 2015

Journal of Pharmaceutical Sciences

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Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015

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“…Reliable estimates of the average effective particle density are obtained if there is a sufficiently large size difference between intraparticular pores and interparticular voids. 4 However, the size range of inhalation particles is below the size required for mercury porosimetry and hence, the microparticles used in this study were not suitable for this type of analysis. Furthermore, the method cannot identify the density of individual particles or if the density varies with particle size.…”

Section: Introductionmentioning

confidence: 90%

An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles

Elversson

Andersson

Millqvist‐Fureby³

2007

Journal of Pharmaceutical Sciences

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Compression characteristics of granulated materials: VI. Pore size distributions, assessed by mercury penetration, of compacts of two lactose granulations with different fragmentation propensities

Cited by 38 publications

References 10 publications

Effect of drug substance particle size on the characteristics of granulation manufactured in a high-shear mixer

Effect of drug substance particle size on the characteristics of granulation manufactured in a high-shear mixer

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles

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