以共聚维酮和交联聚维酮为载体的尼莫地平固体分散体物理稳定性和溶出行为研究

Stability and Dissolution Study of Nimodipine Amorphous Solid Dispersion Using Copovidone and Crospovidone as Carriers

关键词:  尼莫地平  共聚维酮  交联聚维酮  固体分散体  喷雾干燥  稳定性  溶出

Key words:  nimodipine  copovidone  crospovidone  solid dispersion  spray drying  stability  dissolution

摘要:

目的 本研究考察二元载体制剂处方中难溶性药物尼莫地平无定形固体分散体(amorphous solid dispersion, ASD)及其片剂的体外溶出度和物理稳定性并优化处方。方法 以共聚维酮(Copovidone, PVPVA)和交联聚维酮(Crospovidone, PVPP)作为载体,尼莫地平为模型药,采用极端顶点混合设计处方,通过喷雾干燥技术制备ASD粉末。采用差示扫描量热、傅里叶转换红外光谱法、扫描电镜、偏光显微镜、粉末X射线衍射实验考察制得ASD粉末理化性质和物理稳定性,使用原位光纤技术探究ASD粉末及其片剂的溶出行为。结果 当尼莫地平ASD载药量为20% (w/w),PVPVA含量为25% (w/w),PVPP含量为55% (w/w)时,在1个月的加速条件下保持稳定。用喷雾干燥方法制备的ASD片剂与普通片剂比较具有更快的片剂崩解速度和更高的药物溶出速率。结论 单独使用PVPVA为载体的ASD片剂可能存在崩解时间长,药物溶出慢的问题；而单独使用PVPP为载体制得的ASD片剂能有效解决上述问题,但又存在无定形态药物物理稳定性较差的问题。通过两种聚合物载体组合制备的ASD片剂,既能达到良好的物理稳定性,又能实现快速崩解及释药。

Abstract:

This study aims to investigate the dissolution and physical stability of the amorphous solid dispersion (ASD) containing a poorly soluble drug nimodipine. The binary carriers of copovidione and crospovidone were adopted to formulate the amorphous solid dispersion and the ratio of copovidoine to crospovidione was optimized. Methods Copovidone and crospovidone were selected as the polymeric carriers to prepare nimodipine solid dispersions by spray drying. Extreme vertices mix design was used to design formulations. Differential scanning calorimetry, fourier transform infrared spectroscopy, scanning electron microscope, polarization microscope and powder X-ray diffraction analysis were conducted to investigate the physicochemical properties and physical stability of amorphous solid dispersions. In-situ optical fiber technology was used to test the dissolution behavior of amorphous solid dispersions and their tablets. RESULTS When the drug loading was 20% w/w, the contents of PVPVA and PVPP was 25% w/w and 55% w/w respectively, amorphous solid dispersion remained physically stable during accelerated stability test. The prepared amorphous solid dispersion tablets exhibited shorter disintegration rate and faster drug dissolution rate. CONCLUSION When copovidone alone is adopted as the amorphous solid dispersion carrier, the ASD tablets have long disintegration time and slow drug dissolution; whereas if crospovidone is used as the carrier, the amorphous drug is not stable. The combination of copovidone and crospovidone as the ASD carrier can achieve better physical stability of amorphous drug, and the prepared ASD tablets show shorter disintegration time and faster drug dissolution.