Structure formation and characterization of injectable drug loaded biodegradable devices: In situ implants versus in situ microparticles
Structure formation and characterization of injectable drug loaded biodegradable devices: In situ implants versus in situ microparticles
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DOI：
10.1016/j.ejps.2008.03.004
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发表时间：
2008-07-03
影响因子：
4.6
通讯作者：
Bodmeier, R.
中科院分区：
文献类型：
--
作者：
Kranz, H.;Bodmeier, R.
该研究的目的是研究影响局部麻醉剂盐酸布比卡因从不同的原位形成的可生物降解的药物输送装置释放的关键配方变量。配方包括ISM系统[原位微粒，分散到外部油相的聚丙交酯-溶剂相]和聚丙交酯溶液(原位植入系统)。用Hansen多组分溶解度参数概念测定了生物可降解聚合物聚(D，L-丙交酯)在不同有机溶剂中的溶解度。采用高效液相色谱法，考察了溶剂种类、聚合物浓度、聚合物油相比等因素对聚合物沉淀速率的影响。用扫描电子显微镜(SEM)研究药物释放与沉淀植入物或微粒的表面性质之间的关系。利用Hansen多组分溶解度参数概念，找到了制备N-甲基-2-吡咯烷酮(NMP)、二甲基亚砜(DMSO)和2-吡咯烷酮等原位形成药物释放系统的合适溶剂。将聚合物溶液(原位植入物)注入到水介质中导致了快速的溶剂/非溶剂交换。由此得到的原位植入物是多孔的，从而解释了药物最初快速释放的原因。扫描电子显微镜测量表明，当与释放介质接触时，ISM体系的内部聚合物相凝固并形成微粒。由于外部油相的存在，溶剂从ISM释放到缓冲介质中的速度比聚合物溶液慢得多。随着聚合物浓度的增加和聚合物/油相比的降低，ISM体系在磷酸盐缓冲液中的溶剂释放量减少。所使用的溶剂类型也影响溶剂的释放。较慢的溶剂释放到水介质中导致更少的多孔微粒，从而解释了与聚合物溶液相比，ISM系统的初始药物释放减少的原因。(C)2008爱思唯尔B.V.保留所有权利。
The objective of the study was to investigate key formulation variables affecting the release of bupivacaine hydrochloride, a local anesthetic, from different in situ forming biodegradable drug delivery devices. The formulations included ISM systems [in situ microparticles, a poly(lactide)-solvent phase dispersed into an external oil phase] and poly(lactide) solutions (in situ implant systems). The solubility of the biodegradable polymer poly(D,L-lactide) (PLA) in various organic solvents was determined using the Hansen multicomponent solubility parameter concept. The solvent release from ISM and polymer solutions into phosphate buffer which influences the polymer precipitation rate was investigated as a function of the type of solvent, polymer concentration and polymer:oil phase ratio by using a HPLC assay. Scanning electron microscopy (SEM) was performed in order to relate the drug release to the surface proper-ties of the precipitated implants or microparticles. Suitable solvents for the preparation of the in situ forming drug delivery systems, such as N-methyl-2-pyrrolidone (NMP), dimethylsulfoxide (DMSO) and 2-pyrrolidone were found using the Hansen multicomponent solubility parameter concept. The injection of the polymer solutions (in situ implants) into the aqueous medium led to a rapid solvent/non-solvent exchange. The resulting in situ implants were porous, thus explaining the rapid initial drug release. Upon contact with the release medium, the internal polymer phase of the ISM system solidified and formed microparticles as shown by SEM measurements. Due to the presence of an external oil phase the solvent release into the buffer medium from ISM was significantly slower compared to the polymer solutions. The solvent release of the ISM systems into the phosphate buffer decreased with increasing polymer concentration and decreasing polymer:oil phase ratio. The type of solvent used also affected the solvent release. A slower solvent release into the aqueous medium resulted in less porous microparticles, thus explaining the reduced initial drug release from ISM systems compared to the polymer solutions. (C) 2008 Elsevier B.V All rights reserved.