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速溶布洛芬-聚乙二醇6000固体分散体的制备与评价

Preparation and evaluation of fast dissolving ibuprofen-polyethylene glycol 6000 solid dispersions.

作者信息

Newa Madhuri, Bhandari Krishna H, Kim Jung-Ae, Yoo Bong-Kyu, Choi Han-Gon, Yong Chul-Soon, Woo Jong-Soo, Lyoo Won-Seok

机构信息

College of Pharmacy, Yeungnam University, Gyongsan, South Korea.

出版信息

Drug Deliv. 2008 Aug;15(6):355-64. doi: 10.1080/10717540801952431.

Abstract

To improve its oral absorption, rapidly dissolving ibuprofen solid dispersions (SD) were prepared in a relatively easy, simple, quick, inexpensive, and reproducible manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). They were evaluated for solubility, in vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. However, no such interactions in the solid state were confirmed by FTIR spectra that showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast-dissolving ibuprofen SDs by low temperature melting method using PEG 6000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.

摘要

为提高布洛芬的口服吸收效果,采用相对简便、快速、廉价且可重复的方式制备了速溶布洛芬固体分散体(SD),并通过扫描电子显微镜(SEM)、差示扫描量热法(DSC)和傅里叶变换红外光谱(FTIR)对其进行表征。对布洛芬在大鼠体内的溶解度、体外释放度和口服生物利用度进行了评估。SEM显示,在熔融和再固化过程中个别表面性质的丧失表明形成了有效的固体分散体。DSC研究中,固体分散体和物理混合物中药物峰的缺失或向较低熔点温度的移动表明存在药物 - 聚合物相互作用的可能性。然而,FTIR光谱显示固体分散体中存在药物晶体,未证实固态中存在此类相互作用。与纯布洛芬相比,布洛芬从大鼠肠道中的固体分散体中更快释放,导致AUC和C(max)显著增加,T(max)显著降低。本研究的初步结果表明,以聚乙二醇6000作为可熔融亲水性聚合物载体,通过低温熔融法制备速溶布洛芬固体分散体可能是提高布洛芬溶解度、溶出度和吸收速率的一种有前景的方法。

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