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Pharm Res. 2017 Sep;34(9):1805-1816. doi: 10.1007/s11095-017-2188-1. Epub 2017 Jun 15.

Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds.

Author information

1
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, Sweden.
2
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, Sweden. christel.bergstrom@farmaci.uu.se.

Abstract

PURPOSE:

To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.

METHODS:

The IDR and apparent solubility (Sapp) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the μDISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound. Powder and disc dissolution were performed and compared to the IDR of the controlled suspensions.

RESULTS:

The IDR values obtained from the controlled suspensions were in excellent agreement with IDR from disc measurements. The method used low amount of compound (μg-scale) and the experiments were completed within a few minutes. The IDR values ranged from 0.2-70.6 μg/min/cm2 and the IDR/Sapp ratio ranged from 0.015 to 0.23. This ratio was used to indicate particle size sensitivity on intestinal concentrations reached for poorly water-soluble compounds.

CONCLUSIONS:

The established method is a new, desirable tool that provides the means for rapid and highly accurate measurements of the IDR and apparent solubility in biorelevant dissolution media. The IDR/Sapp is proposed as a measure of particle size sensitivity when significant solubilization may occur.

KEYWORDS:

apparent solubility; controlled suspensions; dissolution-limited drug absorption; intrinsic dissolution rate; particle size reduction

PMID:
28620887
PMCID:
PMC5533823
DOI:
10.1007/s11095-017-2188-1
[Indexed for MEDLINE]
Free PMC Article

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