Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels University, Chennai - 600117, India.
Biopharm Drug Dispos. 2010 Oct;31(7):407-27. doi: 10.1002/bdd.722.
The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span-85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41-80 µm. The swelling index was in the range 0.37-0.82 and the entrapment efficiency range was 51-75% for all the formulations. The optimised batch ACM(13) released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non-Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti-inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis.
本研究旨在开发新型的结肠定位给药系统。非甾体抗炎药（NSAID） 醋氯芬酸成功包封于壳聚糖微球中。通过改变壳聚糖、司盘 85 的比例、搅拌速度和戊二醛的用量，制备了不同的制剂。SEM 研究表明微球具有光滑的表面。通过傅里叶变换红外（FTIR）光谱和差示扫描量热法（DSC）对微球进行了表征，以确认药物与聚合物之间不存在化学相互作用，并了解微球结构的形成。对微球进行了粒径、包封效率、载药量、黏膜黏附研究、稳定性研究、体外和体内药物释放研究。通过激光光散射技术测量的粒径为 41-80μm 平均粒径。溶胀指数在 0.37-0.82 范围内，所有制剂的包封效率范围为 51-75%。优化批次 ACM(13)在含有大鼠盲肠内容物的 SCF 中 8 小时释放 83.6%，24 小时释放 104%。Eudragit 包衣壳聚糖微球防止了醋氯芬酸在胃和小肠的生理环境中的释放，在结肠中释放了 95.9±0.34%。就释放动力学而言，数据与 Higuchi 模型拟合最好，表现为零级释放和非 Fickian 扩散机制。体内研究结果表明，醋氯芬酸微球在大鼠体内表现出醋氯芬酸的延长作用，并产生显著的抗炎作用。本研究的结果表明，壳聚糖微球有望用于醋氯芬酸的结肠靶向，以与类风湿关节炎的时间生物学症状同步。
