Hydrophilic and hydrophobic cyclodextrins in a new sustained release oral formulation of nicardipine: in vitro evaluation and bioavailability studies in rabbits
Hydrophilic and hydrophobic cyclodextrins in a new sustained release oral formulation of nicardipine: in vitro evaluation and bioavailability studies in rabbits
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DOI：
10.1016/s0168-3659(02)00465-0
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发表时间：
2003-02-14
影响因子：
10.8
通讯作者：
Veiga, FJB
中科院分区：
文献类型：
--
作者：
Fernandes, CM;Ramos, P;Veiga, FJB
本文研究了在尼卡地平（NC）控释中使用环糊精（CD）复合物的可行性，以期扩大这些载体的药物应用范围。对于快速释放级分，使用亲水性β-环糊精衍生物（羟丙基-β-环糊精）以形成水溶性复合物。对于缓释部分，使用三乙酰基-β-环糊精（TAbetaCD）来提供具有适当疏水性的复合物。通过对各组分按不同配比进行组合，设计出最佳处方。在模拟胃液（pH 1.2）和肠液（pH 6.8）中考察了复合物及其混合物的释放行为。制剂在初始阶段快速释放药物，随后缓慢释放。随着NC/TAbetaCD复合物用量的增加，药物释放速率明显减慢。当NC给予家兔时，其吸收非常迅速，消除半衰期短，而两种选定制剂的血浆水平维持时间较长。与NC/TAbetaCD复合物相比，药物生物利用度显著提高，尤其是在施用亲水性和疏水性复合物的混合物后。结果表明，亲水性和疏水性CD复合物的关键组合，在适当的比例，可能是一个有前途的药物传递系统，具有较长的治疗效果加上更平衡的生物利用度。(C)2002 Elsevier Science B. V.保留所有权利。
The feasibility of using complexes with cyclodextrins (CDs) in nicardipine (NC) controlled delivery has been examined, with a view to extending the pharmaceutical applications spectrum of these carriers. For a fast release fraction, a hydrophilic beta-cyclodextrin derivative (hydroxypropyl-beta-cyclodextrin) was employed to form a water-soluble complex. For the sustained-releasing portion, triacetyl-beta-cyclodextrin (TAbetaCD) was used to provide complexes with appropriate hydrophobicity. An optimal formulation was designed by the combination of each fraction in different mixing ratios. The release behaviour of the complexes, as well as of their mixtures, was examined in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids. The formulations released the drug rapidly at the initial stage, followed by a slow release. The drug release rate was markedly retarded in the increasing order of the amount of NC/TAbetaCD complex. When NC was administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma levels was obtained for the two selected formulations. The drug bioavailability was considerably improved especially after the administration of the mixture of hydrophilic and hydrophobic complexes, when compared with the NC/TAbetaCD complex. The results suggested that the critical combination of hydrophilic and hydrophobic CDs complexes, in appropriate ratios, could be a promising drug delivery system with a prolonged therapeutic effect coupled with a more balanced bioavailability. (C) 2002 Elsevier Science B.V. All rights reserved.