Injectable polyanhydride granules provide controlled release of water-soluble drugs with a reduced initial burst.
Injectable polyanhydride granules provide controlled release of water-soluble drugs with a reduced initial burst.
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可注射的聚酐颗粒可控制水溶性药物的释放，并减少初始爆发。
DOI：
10.1002/jps.2600830104
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发表时间：
1994
影响因子：
3.8
通讯作者：
Langer,R
中科院分区：
文献类型：
--
作者：
Tabata,Y;Domb,A;Langer,R
□开发了用于制备可注射尺寸的聚酸酐颗粒的方法。由此产生的颗粒允许几乎恒定的释放低分子量的水溶性药物，而没有最初的爆发。所用的聚酸酐是聚（脂肪酸二聚体）、聚（癸二酸）和它们的共聚物。以染料酸性橙子63和对硝基苯胺为药物模型化合物。聚合物降解和药物释放的磁盘和不同大小的颗粒的共聚物含有药物，制备的油包水（W/O）乳液的方法，进行了比较与那些由通常的压缩方法制备的设备。在W/O乳化法中，药物水溶液和聚合物-氯仿溶液的混合物通过探针超声乳化以制备非常细的W/O型乳剂。将通过冷冻干燥W/O乳液获得的粉末压制成圆盘。在压缩方法中，将药物与聚合物机械混合，并将混合物压缩成圆盘。研磨所得圆盘以制备不同尺寸的颗粒。颗粒包封超过95%的药物，无论制备方法如何。这两种方法都可以有效地制备能够控制药物释放而没有任何初始爆发的聚合物圆盘。然而，当颗粒尺寸减小到可注射尺寸（直径，<150 μ π ι）时，在两种制备方法之间观察到药物释放曲线的较大差异。通过W/O乳液方法获得的可注射颗粒显示出几乎恒定的药物释放，而没有任何大的初始突释，与通过压缩方法制备的那些相比，无论药物类型如何。颗粒的降解研究表明，两种方法之间颗粒基质本身的降解特征无差异。通过压缩方法制备的聚合物盘的光学显微镜观察表明染料岛在整个基质中的不均匀分布。相比之下，通过W/O乳液方法制备的装置实现了染料和聚合物的高度均匀混合。因此，药物在整个聚合物基质中的这种高度均匀分布可能导致通过W/O乳液方法获得的可注射颗粒的药物释放的初始突释减少。
□ A method for preparing poiyanhydride granules of an injectable size was developed. The resulting granules permitted a nearly constant release of low-molecular-weight, water-soluble drugs without an initial burst. The polyanhydrides used were poiy(fatty acid dimer), poly(sebacic acid), and their copolymers. The dyes acid orange 63 and p-nitroaniline were used as model compounds for drugs. Polymer degradation and drug release for disks and variously sized granules of copolymers containing drugs, prepared by a water-in-oil (W/O) emulsion method, were compared with those for devices prepared by the usual compression method. In the W/O emulsion method, a mixture of aqueous drug solution and polymer-chloroform solution was emulsified by probe sonication to prepare a very fine W/O emusion. The powder obtained by freeze-drying of the W/O emulsion was pressed into circular disks. In the compression method, the drug was mechanically mixed with the polymer, and the mixture was compressed into circular disks. The resulting disks were ground to prepare granules of different sizes. The granules encapsulated more than 95% of the drug, irrespective of the preparation method. Both methods were effective in preparing polymer disks capable of controlled drug release without any initial burst. However, as the granule size decreased to an injectable size (diameter, <150 pm), a large difference in the drug release profile was observed between the two preparation methods. The injectable granules obtained by the W/O emulsion method showed nearly constant drug release without any large initial burst, in contrast to those prepared by the compression method, irrespective of the drug type. Degradation studies of the granules demonstrated no difference in the degradation profile of the granule matrix itself between the two methods. Light microscopic observations of polymer disk prepared by the compression method indicated a nonuniform distribution of dye islands throughout the matrix. In contrast, a highly homogeneous mixing of dye and polymer was achieved for devices prepared by the W/O emulsion method. It is therefore possible that this highly uniform distribution of drug throughout the polymer matrix leads to a reduced initial burst in drug release from the injectable granules obtained by the W/O emulsion method.