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Improvement of Solubility and Oral Bioavailability of a Poorly Water-Soluble Drug, TAS-301, by Its Melt-Adsorption on a Porous Calcium Silicate

Improvement of Solubility and Oral Bioavailability of a Poorly Water-Soluble Drug, TAS-301, by Its Melt-Adsorption on a Porous Calcium Silicate

Masahiro Kinoshita, Kazuhiko Baba, Atushi Nagayasu, Kanoo Yamabe, Takashi Shimooka, Yoh'ichiro Takeichi, Mami Azuma, Hitoshi Houchi, Kazuo Minakuchi

J Pharm Sci. 2002 Feb;91(2):362-70.

PMID: 11835196

Abstract:

The aim of the present study was to improve the solubility and oral bioavailability of a poorly water-soluble drug, 3-bis(4-methoxyphenyl) methylene-2-indolinone (TAS-301), by its melt-adsorption on a porous calcium silicate, Florite RE (FLR), without any solvents. The melt-adsorbed products were prepared by two methods: the small-scale batch method and the twin screw extruder method. The drug was melted and adsorbed on FLR (i.e., "melt-adsorption"), above its melting point. Crystallinity of the drug in the melt-adsorbed product was estimated by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis. The dissolution test was conducted by the JP XIII paddle method. Oral absorption of the melt-adsorbed product was studied in fasted and fed dogs. The melt-adsorbed products prepared by the two methods were in powder forms. The drug existed in an amorphous state in the product and hardly recrystallized even after storing at a stressed condition (60 degrees C/80% RH for 3 days). The TAS-301 dissolution rate from the melt-adsorbed product was markedly enhanced compared with drug crystals. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of the drug after dosing the melt-adsorbed product were significantly greater than those after dosing the drug crystals. The solubility and bioavailability of TAS-301 were improved by its melt-adsorption on FLR. The present findings suggest melt-adsorption is a useful technique for improving solubility and bioavailability of poorly water-soluble drugs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP193620698	TAS-301		193620-69-8	Price

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