Preparation of a co-amorphous form of bexarotene-PVP-K30 and evaluation in rats
10.16438/j.0513-4870.2019-0857
- VernacularTitle:蓓萨罗丁-聚乙烯吡咯烷酮共无定型物制备及在SD大鼠体内评价
- Author:
Shu-yue REN
1
;
Ling-tai JIAO
2
;
Hao-ying YU
1
;
Jing-rong WANG
1
;
Jun-ke SONG
1
;
Ting-ting LÜ
1
;
Yang LÜ
2
;
Shi-ying YANG
2
;
Lan SUN
1
;
Guan-hua DU
1
Author Information
1. Beijing Key Laboratory of Drug Target Research and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
bexarotene;
bexarotene-PVP-K30 co-amorphous;
LC-MS;
pharmacokinetic;
tissues distribution
- From:
Acta Pharmaceutica Sinica
2020;55(5):1015-1021
- CountryChina
- Language:Chinese
-
Abstract:
Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
