du Toit Lisa C, Pillay Viness, Choonara Yahya E, Iyuke Sunny E
Division of Pharmaceutics, Department of Pharmacy and Pharmacology, University of Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
AAPS PharmSciTech. 2008;9(1):174-81. doi: 10.1208/s12249-007-9016-6. Epub 2008 Jan 25.
The purpose of this study was to develop a drug-loaded nanosystem that has the ability to achieve flexible yet rate-controlled release of model drug isoniazid (INH) employing either an aqueous or emulsion-based salting-out approach. Formulation conditions were aimed at reducing the polymeric size with subsequent rate-modulated INH release patterns from the polymeric nanosystem. The emulsion-based salted-out nanosystems had particle sizes ranging from 77-414 nm and a zeta potential of -24 mV. The dispersant dielectric constant was set at 78.5 and a conductivity of 3.99 mS/cm achieved. The reduced nanosystem size of the aqueous-based approach has demonstrated an intrinsically enhanced exposure of methacrylic acid-ethyl acrylate to zinc sulphate which was employed as a crosslinking reagent. This resulted in robustly interconnected polymeric supports in which INH was efficiently embedded and subsequently released. The multi-layer perceptron data obtained showed that the aqueous and emulsion-based salting out approaches had Power (law) (MSE = 0.020) and Linear (MSE = 0.038) relationships, respectively. Drug release from the nanosystems occurred in two phases with an initial burst-release in aqueous-based nanosystems (30-100%) and significantly lower bursts observed in emulsion-based nanosystems (20-65%) within the first 2 h. This was followed by a gradual exponential release phase over the remaining 12 h. The nanosystems developed demonstrated the ability to control the release of INH depending on the formulation approach adopted.
本研究的目的是开发一种载药纳米系统,该系统能够采用水相或乳液基盐析方法实现模型药物异烟肼(INH)的灵活且可控速率释放。配方条件旨在减小聚合物尺寸,从而使聚合物纳米系统呈现出速率调节的INH释放模式。乳液基盐析纳米系统的粒径范围为77 - 414 nm,zeta电位为 -24 mV。分散剂介电常数设定为78.5,电导率达到3.99 mS/cm。水相方法制备的纳米系统尺寸减小,这表明甲基丙烯酸 - 丙烯酸乙酯与用作交联剂的硫酸锌之间的内在接触增强。这导致形成了坚固互连的聚合物载体,INH被有效地嵌入其中并随后释放。获得的多层感知器数据表明,水相和乳液基盐析方法分别具有幂(律)关系(均方误差 = 0.020)和线性关系(均方误差 = 0.038)。纳米系统中的药物释放分两个阶段进行,水相纳米系统在前2小时内出现初始突释(30 - 100%),而乳液基纳米系统在前2小时内观察到的突释明显较低(20 - 65%)。随后在剩余的12小时内进入逐渐的指数释放阶段。所开发的纳米系统证明了能够根据所采用的配方方法控制INH的释放。