A comparison of the inter- and intragranular drug migration in tray- and freeze-dried granules and compacts

Filip Kiekens, Romána Zelkó, Jean Paul

Research output: Article

12 Citations (Scopus)


The influence of the drying process (tray- or freeze-drying), the granulation liquid viscosity, and the drying time during tray-drying on the inter- and intragranular migration of both a water-soluble and a poorly water-soluble compound in a granulation mass and in a compact were quantitatively assessed. Quinidine bisulfate (QBS) and riboflavin (RB) were mixed with a model excipient (glass microspheres) and granulated with an aqueous povidone solution. The drug concentration at different locations inside the granulated mass and in the compacts after drying was determined spectrophotometrically. The RB distribution in the compacts was more homogeneous than the QBS distribution. For both drugs it was clear that the intragranular migration decreased as the granulation liquid viscosity increased. The RB distribution in oven-dried granulation masses showed no migration problem, whereas the QBS samples were characterized by drug- enriched outer layers and drug-depleted inner regions, indicating a strong migration phenomenon. The drug distribution in all freeze-dried samples was homogeneous. A homogeneous distribution of a small-dosed water-soluble and a water-insoluble drug in granules and in compacts was obtained by the use of freeze-drying. The intragranular migration of QBS was prevented by the use of twice the amount of binder compared to that in RB compacts.

Original languageEnglish
Pages (from-to)415-420
Number of pages6
JournalPharmaceutical Development and Technology
Issue number3
Publication statusPublished - aug. 5 1999

ASJC Scopus subject areas

  • Pharmaceutical Science

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