Engineered microcrystals for direct surface modification with layer-by-layer technique for optimized dissolution
Engineered microcrystals for direct surface modification with layer-by-layer technique for optimized dissolution
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DOI：
10.1016/j.ejpb.2004.05.008
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Sukhorukov, GB
中科院分区：
文献类型：
--
作者：
Shenoy, DB;Sukhorukov, GB
本研究涉及两步处方开发技术-空间稳定药物微晶的合成，然后通过顺序静电吸附进行直接表面改性。在稳定剂的存在下，通过pH诱导的再沉淀产生稳定的纳洛芬微晶。通过生物相容性聚电解质（PE）的逐层组装实现顺序层生长，并使用微电泳进行注册。使用共聚焦激光扫描显微镜（CLSM）和扫描电子显微镜（SEM），其特征在于包覆的胶体。通过PE扩散屏障的药物的体外控制释放模式进行了研究，使用在生理pH值为7.4的扩散池组件，在冷冻干燥之前和之后。热力学稳定的naplisen微晶获得协会和平均长度为15 μ m，和zeta电位为-37.5 mV，并有效地使用生物相容性的多糖/蛋白质为基础的PE表面改性。每个层的充分电荷反转是明显的，表明随着连续沉积循环的层生长。如在CLSM和SEM下观察到的，涂层是完整且均匀的。体外释放研究表明，复合包衣中PE的化学计量比及其分子结构在形成扩散屏障方面起着重要作用，从而有效地控制了药物核心的溶出速率（比裸晶体低50%）。释放曲线符合零级释放动力学。这种新的制剂技术能够以稳定的、组织相容的形式施用高浓度的水不溶性药物，同时提供持续释放。(C)2004 Elsevier B. V.保留所有权利。
This investigation relates to a two-step formulation development technique-synthesis of sterically stabilized drug microcrystals followed by direct surface modification by sequential electrostatic adsorption. Stable microcrystals of naproxen were produced by pH-induced reprecipitation in presence of a stabilizer. Sequential layer growth was achieved by the layer-by-layer assembly of biocompatible polyelectrolytes (PEs) and was registered using microelectrophoresis. The coated colloids were characterized using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The in vitro controlled release pattern of the drug through the PE diffusion barrier was studied using a diffusion cell assembly at physiological pH of 7.4, both before and after freeze-drying. Thermodynamically stable naproxen microcrystals were obtained by association and had a mean length of 15 mum, and a zeta potential of -37.5 mV and were surface modified efficiently using biocompatible polysaccharide/protein-based PEs. Sufficient charge reversal with each layer was evident indicating layer growth with successive deposition cycles. The coating was complete and homogeneous as visualized under CLSM and SEM. The in vitro release study revealed that the stoichiometry of PEs in the complex coating and its molecular architecture played important roles in forming the diffusion barrier, which offered efficient control of the dissolution rate of drug core (up to 50% lower than bare crystal). The release profile fitted zero order release kinetics. This novel formulation technique enables administration of high concentrations of water insoluble drugs in a stable, tissue compatible form, simultaneously affording sustained release. (C) 2004 Elsevier B.V. All rights reserved.