Investigation of physicochemical properties and in-vitro in-vivo evaluation of agomelatine polymorphs  

作　　者：Wei Du Yuefang Zhou Yafei Gong Chunshun Zhao 

机构地区：[1]Sun Yat-sen University,Guangzhou 510006,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2013年第3期181-190,共10页亚洲药物制剂科学（英文）

基　　金：The authors acknowledge the financial support received from the National Science and Technology Major Projects for Major New Drugs Innovation and Development of China(No.2009ZX09501-022).

摘　　要：In the present study,Form I,Form II and Form III of agomelatine were prepared to investigate the variability of polymorphs,then the in-vitro in-vivo correlation were established.The presence of three polymorphs of agomelatine was corroborated through studies by XRPD,TGA and DSC.All the forms obtained were then subjected to the powder and intrinsic dissolution tests.The IDR ranked in the order of Form III>Form I>Form II.Form I and Form III both underwent solvent-mediated phase transformation(SMPT)to Form II during dissolution and the transition points were 62 and 45 min,respectively.Pharmacokinetic profiles were acquired after oral administration of tablets,showing that the ka and AUC0e12 h of Form I,Form II,Form III were 0.58
0.11,0.34
0.05,0.74
0.07 h1 and 296.25
49.39,186.05
45.93,331.16
54.74 ng*h/ml,respectively.Good linearities between IDR and ka,IDR and AUC were established,suggesting that the agomelatine polymorphic forms with faster dissolution rates in-vitro would increase the rate and extent of oral absorption in-vivo.These results demonstrated that IDR was predictive in estimating the relative bioavailability of agomelatine polymorphic forms.

关 键 词：AGOMELATINE POLYMORPHS Intrinsic dissolution rate PHARMACOKINETICS IVIVC 

分 类 号：O63[理学—高分子化学]