کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2498563 1556758 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of physicochemical properties and in-vitro in-vivo evaluation of agomelatine polymorphs
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Investigation of physicochemical properties and in-vitro in-vivo evaluation of agomelatine polymorphs
چکیده انگلیسی

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 AUC0–12 h of Form I, Form II, Form III were 0.58 ± 0.11, 0.34 ± 0.05, 0.74 ± 0.07 h−1 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Asian Journal of Pharmaceutical Sciences - Volume 8, Issue 3, June 2013, Pages 181–190
نویسندگان
, , , ,