Formulation studies and in vivo evaluation of a flurbiprofen-hydroxypropyl β-cyclodextrin system
Formulation studies and in vivo evaluation of a flurbiprofen-hydroxypropyl β-cyclodextrin system
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DOI：
10.1081/pdt-200049687
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Nagarsenker, MS
中科院分区：
文献类型：
--
作者：
Govindarajan, R;Nagarsenker, MS
本研究的目的是1)研究氟比洛芬（FPN)-羟丙基-环糊精（HP β CD）固体分散体（SD）在大鼠体内的优势，2）研究影响SD制剂药物释放的因素，3)评价药物以SD形式给药时的药动学特征。在人类身上。FPN在水和溶解介质中的溶解度被评价为HP β CD浓度的函数。采用稀NH3共蒸发法制备SD，并在大鼠体内进行评价。研究了SD片剂和胶囊在pH为7.2的模拟胃液和磷酸盐缓冲液中的释药情况。以SD方式给药时，评估了药物在人体中的生物利用度。HP β - CD增强了药物的溶解度，SD提高了药物在大鼠体内的生物利用度，降低了药物的溃疡性。所用赋形剂的类型影响药片的药物释放。存在微晶纤维素，一种亲水性聚合物赋形剂。导致含HP β cd片剂的水吸收和凝胶状结构的稳定。这对药物释放有不利影响。SD填充胶囊的释放度与普通SD粉末相当。药物- hp - β - CD在水中的关联常数远低于文献报道的值。生物利用度（在关联常数较高的情况下可能会受到影响）通过给人服用sd填充胶囊而增强。
The purpose of this study was 1) to investigate in vivo advantages of a flurbiprofen (FPN)-hydroxypropyl beta-cyclodextrin (HP beta CD) solid dispersion (SD) in rats, 2) to study factors affecting the drug release from SD formulations, and 3) to evaluate the pharmacokinetic profile of the drug when administered as SD. in humans. The solubility of FPN in water and dissolution media was evaluated as a function of HP beta CD concentration. The SD was prepared by coevaporation from dilute aqueous NH3 and evaluated in rats. The release of the drug from tablet formulations and capsules of SD was studied in simulated gastric fluid and phosphate buffer, pH 7.2. The bioavailability of drug when administered as SD was evaluated in humans.HP beta CD enhanced the solubility of the drug, and SD improved bioavailability and reduced ulcerogenicity of the drug in rats. The type of excipient used affected drug release from tablets. Presence of microcrystalline cellulose, a hydrophilic polymeric excipient. resulted in uptake of water and stabilization of the resulting gels-like structure of HP beta CD-containing tablets. This adversely affected drug release. The release from capsules filled with SD was comparable to that obtained from plain SD powder. The drug-HP beta CD association constant in water was much lower than the values reported in literature. The bioavailability (which could suffer in case of higher association constant) was enhanced on administration of SD-filled capsules to humans.