阿奇霉素-离子交换树脂复合物的制备及其掩味与调控释药作用

Preparation of azithromycin-ion exchange resin complexes for taste-mask⁃ing and controlled drug release

为掩盖阿奇霉素(azithromycin,AZI)苦味和个性化调控药物释放速度以减少胃肠道刺激,分别以羟丙基纤维素(hydroxypropyl cellulose,HPC)和尤特奇RS100修饰制备速释型AZI-AmberliteTM IRP64/HPC和缓释型AZI-AmberliteTM IRP69/RS100进而组合以实现控制释放。对AZI-离子交换树脂复合物的载药量、药物利用率进行测定,通过差示扫描量热分析和X射线衍射对AZI-离子交换树脂复合物进行结构表征,测定其润湿度、掩味效果、体外溶出和释放行为。结果显示,形成的AZI-离子交换树脂复合物改变了药物原有的结晶状态,2.5%HPC修饰的AZI-AmberliteTM IRP64/HPC和0.5%RS100修饰的AZI-AmberliteTM IRP69/RS100掩味效果良好,两者以对应AZI含量为13∶67的比例组合可以实现AZI在前10 min的快速释放和后期的6 h内平稳释药。结果表明,经表面修饰制得的AZI-离子交换树脂复合物及其组合物能够掩盖AZI苦味并可实现对药物释放速度的灵活调节,为AZI新制剂的研究开发奠定了基础。

In order to mask the bitterness of azithromycin(AZI)and individually regulate the drug release rate to reduce gastrointestinal irritation,immediate-release AZI-AmberliteTM IRP64/HPC and delayed-release AZIAmberliteTM IRP69/RS100 were prepared by modifying with hydroxypropyl cellulose(HPC)and Eudragit RS100,respectively,and further combined to achieve controlled release.The drug loading and drug utilization rate of AZI-ion exchange resin complexes were measured;the structure of AZI-ion exchange resin complexes was characterized by differential scanning calorimetry and X-ray diffraction;and the wetting humidity,odor masking effects,in vitro dissolution and release behaviors were determined.The results showed that the formation of AZIion exchange resin complexes changed the original crystallization state of the drug,that the 2.5%HPC-modified AZI-AmberliteTM IRP64/HPC and the 0.5%RS100-modified AZI-AmberliteTM IRP69/RS100 demonstrated good taste masking effect,and that their combination in the drug content ratio of 13∶67 achieved the expected drug release behavior,i.e.rapid release of AZI in the first 10 min and smooth release in the later 6 h.These results indicated that the AZI-ion exchange resin complexes prepared by surface modification and their composites could mask the bitterness of AZI and realize the flexible adjustment of drug release rate,which lays the foundation for the research and development of new AZI preparations.