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Application of the solid dispersion method to the controlled release of medicine. IV. Precise control of the release rate of a water soluble medicine by using the solid dispersion method applying the difference in the molecular weight of a polymer.

Abstract：

:Solid dispersions were prepared by the evaporation of ethanol after dissolving into ethanol a water soluble medicine (oxprenolol hydrochloride (OXP)), four grades of water insoluble ethylcellulose (EC) and four grades of water soluble hydroxypropyl cellulose (HPC), both having different molecular weights. The precise control of the release rat of a water soluble medicine by applying the difference in the molecular weight of polymers was attempted. The pore size distribution in solid dispersion granules was measured before and after the dissolution test by mercury intrusion porosimetry to clarify the mechanism of medicine release from the granules when the molecular weights of polymers were different. The state of medicine in the solid dispersions was analyzed by thermal analysis and X-ray diffractometry. Although the difference was slight, the release rate of OXP from the granules of the OXP-HPC system decreased as the molecular weight of HPC increased. The release behavior of OXP in the OXP-EC system was scarcely affected by the molecular weight of EC. However, in the OXP-EC-HPC system, the release rate markedly decreased with a larger molecular weight of EC. It was thought from the results of the pore size distribution that there were two types of release routes for OXP; dissolving directly into the dissolution medium and diffusing in the swelled HPC phase, caused by the addition of HPC. The decrease in the release rate of OXP in the OXP-EC-HPC system was caused by the increase in the ratio of OXP dissolving via the latter route, occurring with a larger molecular weight of EC. These results suggest that it is feasible to precisely control the release of a water soluble medicine by varying the molecular weight of the polymers in the solid dispersion.

journal_name

Chem Pharm Bull (Tokyo)

journal_title

Chemical & pharmaceutical bulletin

authors

Yuasa H,Ozeki T,Kanaya Y,Oishi K

doi

10.1248/cpb.41.933

subject

Has Abstract

pub_date

1993-05-01 00:00:00

pages

933-6

issue

eissn

0009-2363

issn

1347-5223

journal_volume

pub_type

杂志文章

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Application of the solid dispersion method to the controlled release of medicine. IV. Precise control of the release rate of a water soluble medicine by using the solid dispersion method applying the difference in the molecular weight of a polymer.