Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: Establishment of level A IVIVC
Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: Establishment of level A IVIVC
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DOI：
10.1016/j.jconrel.2008.03.016
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发表时间：
2008-07-02
影响因子：
10.8
通讯作者：
Mashru, Rajashree C.
中科院分区：
文献类型：
--
作者：
Sankalia, Jolly M.;Sankalia, Mayur G.;Mashru, Rajashree C.
本研究的目的是在存在一系列处方/生产变更的情况下，检查格列吡嗪亲水性缓释基质的A级体外-体内相关性（IVIVC），具有可接受的内部可预测性。研究了乙基纤维素、微晶纤维素、羟丙基甲基纤维素、黄原胶、瓜尔豆胶、淀粉1500和乳糖的聚合物共混物对体外释放曲线的影响，并拟合了各种释放动力学模型。水吸收动力学与扫描电子显微镜（SEM）进行了支持药物释放机制。通过比较白色白化病兔单次经口给药研究后优化（M-24）和市售（Glytop-2.5 SR）制剂的药代动力学参数，建立IVIVC。基质M-19（黄原胶：MCC PH 301，70：40）和M-24（黄原胶：HPMC K4 M：淀粉1500，70：25：15）显示格列吡嗪在所有时间点的释放均在预定限制范围内，分别符合Korsmeyer-Peppas和零级释放机制。Kopcha模型显示黄原胶是负责扩散释放曲线的主要赋形剂，并得到SEM和溶胀研究的进一步支持。具有可接受的预测误差限度（低于15%）的显著水平A IVIVC能够根据其体外释放曲线预测体内性能。得出的结论是，适当选择具有释放速率调节剂赋形剂的速率控制聚合物将决定总体释放曲线。持续时间和机制从直接压缩矩阵。(c)2008 Elsevier B. V.保留所有权利。
The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/ manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum,guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile. duration and mechanism from directly compressed matrices. (c) 2008 Elsevier B.V. All rights reserved.