Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5521363 | European Journal of Pharmaceutics and Biopharmaceutics | 2017 | 13 Pages |
â¢Extruded milled griseofulvin (GF, drug) suspensions along with additional polymers.â¢Formed HPC-based nanocomposite and Soluplus-based amorphous solid dispersion (ASD).â¢Compared dissolution response under non-supersaturating conditions (low drug dose).â¢Drug nanocrystals in the nanocomposite dissolved faster than amorphous drug in ASD.â¢Showed the impact of drug particle size and extrudate (matrix) size on dissolution.
Nanoextrusion was used to produce extrudates of griseofulvin, a poorly water-soluble drug, with the objective of examining the impact of drug particle size and polymeric matrix type-size of the extrudates on drug dissolution enhancement. Hydroxypropyl cellulose (HPC) and Soluplus® were used to stabilize wet-milled drug suspensions and form matrices of the extrudates. The wet-milled suspensions along with additional polymer (HPC/Soluplus®) were fed to a co-rotating twin-screw extruder, which dried the suspensions and formed various extrudates. The extrudates were dry-milled and sieved into samples with two different sizes. A wet-milled suspension was also spray-dried in comparison to nanoextrusion. Due to differences in polymer-drug miscibility, two forms of the drug were prepared: extrudates with nano/micro-crystalline drug particles dispersed in the HPC matrix as a secondary phase (nano/microcomposites) and extrudates with amorphous drug molecularly dispersed within the Soluplus® matrix (amorphous solid dispersion, ASD). Under non-supersaturating conditions in the dissolution medium, drug nanocrystals in the HPC-based nanocomposites dissolved faster than the amorphous drug in Soluplus®-based ASD. While smaller extrudate particles led to faster drug release for the ASD, such matrix size effect was weaker for the nanocomposites. These findings suggest that nanocrystal-based formulations could outperform ASDs for fast dissolution of low-dose drugs.
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