Formulation of dried lignans nanosuspension with high redispersibility to enhance stability,dissolution,and oral bioavailability

作     者：SHEN Gang CHENG Ling WANG Li-Qiang ZHANG Li-Hong SHEN Bao-De LIAO Wei-Bo LI Juan-Juan ZHENG Juan XU Rong YUAN Hai-Long 

作者机构：Department of PharmacyAir Force General Hospital of PLABeijing 100142China Pharmacy CollegeChengdu University of Traditional Chinese MedicineChengdu 611137China School of Biomedical SciencesHuaqiao UniversityQuanzhou 362021China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2016年第14卷第10期

页      面：757-768页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Key New Drugs Innovation Foundation(No.2015ZX09101025) the National Science Foundation of China(No.81503169) the New Drugs Development Special Foundation of Beijing City of China(No.Z141100002214007) 

主　　题：Herpetospermum caudigerum lignans Nanosuspensions Acid-base neutralization Saturation solubility Dissolution Oral bioavailability 

摘      要：Herpetospermum caudigerum lignans(HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione(HPE) and herpetin(HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL(composed of HPE and HPN) nanosuspensions(HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4%(W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 oC for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC0–t, C_(max), MRT and a decrease in T_(max), compared to the raw drug.. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with p H-dependent solubility.