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使用超临界二氧化碳将非诺贝特负载于介孔二氧化硅上。

Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide.

作者信息

Bouledjouidja Abir, Masmoudi Yasmine, Van Speybroeck Michiel, Schueller Laurent, Badens Elisabeth

机构信息

Aix Marseille Université, CNRS, Centrale Marseille, M2P2 UMR 7340, 13451 Marseille, France.

FORMAC Pharmaceuticals NV, Gaston Geenslaan 1, 3001 Heverlee, Belgium.

出版信息

Int J Pharm. 2016 Feb 29;499(1-2):1-9. doi: 10.1016/j.ijpharm.2015.12.049. Epub 2015 Dec 28.

Abstract

Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.

摘要

低口服生物利用度可通过将难溶性药物制成有序介孔二氧化硅(OMS-L-7)制剂来克服。非诺贝特是一种口服给药的、难溶于水的活性药物成分(API),临床上用于降低血脂水平。非诺贝特通过两种方法载入二氧化硅中:初湿含浸法和超临界浸渍法。本研究考察了载入量的影响以及不同超临界二氧化碳(scCO2)处理条件的影响。目的是提高非诺贝特在二氧化硅中的载入量,同时降低药物的结晶度,从而提高药物的溶解速率及其生物利用度。对两种浸渍工艺在浸渍产率、持续时间以及药物的物理表征方面进行了比较。虽然初湿含浸法在浸渍48小时后可使非诺贝特的载入量达到300mg药物/克二氧化硅,但在16MPa和308K下,超临界浸渍法在120分钟的浸渍时间内可使载入量达到485mg药物/克二氧化硅,且结晶度较低(约1%),与通过溶剂法观察到的结晶度相当。除了提高浸渍效率外,超临界方法还为浸渍提供了一种无溶剂的替代方法。

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