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 ago...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 0.580.11,0.340.05,0.740.07 h1 and 296.2549.39,186.0545.93,331.1654.74 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.展开更多
Oxycodone hydrochloride is a semi-synthetic opioid agonist that provides very effective relief for moderate to severe pain in cancer and post-operative patients. Controlled release oxycodone formulations have been stu...Oxycodone hydrochloride is a semi-synthetic opioid agonist that provides very effective relief for moderate to severe pain in cancer and post-operative patients. Controlled release oxycodone formulations have been studied to enhance the therapeutic effect by providing constant release over the whole dosing interval and improve patient’s convenience by reducing the frequency of administration as well.展开更多
综述具有生物相关性的溶出度方法,以通过理想的体外溶出试验预测体内药动学过程。近年来,研究表明在生物相关性溶出介质中选择合适的溶出装置进行溶出试验得到的溶出曲线能较好地反映其在体内的溶出行为,计算机模拟软件可为建立合理的...综述具有生物相关性的溶出度方法,以通过理想的体外溶出试验预测体内药动学过程。近年来,研究表明在生物相关性溶出介质中选择合适的溶出装置进行溶出试验得到的溶出曲线能较好地反映其在体内的溶出行为,计算机模拟软件可为建立合理的体外溶出度方法提供指导和依据。通过采用合适的生物相关性溶出介质、溶出装置,结合计算机模拟软件可建立A级水平的体内外相关性(in vitro-in vivo correlation,IVIVC),可能代替生物等效性研究。展开更多
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).
文摘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 0.580.11,0.340.05,0.740.07 h1 and 296.2549.39,186.0545.93,331.1654.74 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.
文摘Oxycodone hydrochloride is a semi-synthetic opioid agonist that provides very effective relief for moderate to severe pain in cancer and post-operative patients. Controlled release oxycodone formulations have been studied to enhance the therapeutic effect by providing constant release over the whole dosing interval and improve patient’s convenience by reducing the frequency of administration as well.
文摘综述具有生物相关性的溶出度方法,以通过理想的体外溶出试验预测体内药动学过程。近年来,研究表明在生物相关性溶出介质中选择合适的溶出装置进行溶出试验得到的溶出曲线能较好地反映其在体内的溶出行为,计算机模拟软件可为建立合理的体外溶出度方法提供指导和依据。通过采用合适的生物相关性溶出介质、溶出装置,结合计算机模拟软件可建立A级水平的体内外相关性(in vitro-in vivo correlation,IVIVC),可能代替生物等效性研究。
