摘要
采用粉末X射线衍射(PXRD)分析技术确定了13种药用辅料[淀粉、乳糖、甘露醇、微晶纤维素(MCC)、聚维酮(PVP K30)、羧甲纤维素钠(CMC-Na)、二氧化硅、羧甲淀粉钠(CMS-Na)、低取代羟丙纤维素(L-HPC)、交联羧甲纤维素钠(CC-Na)、微粉硅胶、滑石粉和硬脂酸镁]的晶型状态。结果显示,乳糖、甘露醇、滑石粉和硬脂酸镁为晶态,其他9种为非晶态。考察了各辅料经压片和影响因素试验后的晶型稳定性,并进一步考察各辅料与硫酸氢氯吡格雷原料药物理混合及各物理混合物经影响因素试验后原料药的晶型稳定性。结果表明,淀粉、MCC、二氧化硅、L-HPC、微粉硅胶和滑石粉的晶型稳定性较优,与原料药的相容性相对较好。在高湿试验中,乳糖、甘露醇和硬脂酸镁PXRD图谱发生明显改变,PVP、CMC-Na、CMS-Na和CC-Na因吸湿而呈液态;各辅料与原料药物理混合物中原料药的晶型均发生改变,提示原料药晶型在高湿环境中不稳定。
By powder X-ray diffraction （PXRD） technique, the solid-state forms of 13 pharmaceutical excipients [starch, lactose, mannitol, microcrystalline cellulose （MCC）, povidone （PVP K30）, carboxymethylcellulose sodium （CMC-Na）, silicon dioxide, sodium starch glycolate （CMS-Na）, low-substituted hydroxypropyl cellulose （L-HPC）, croscarmellose sodium （CC-Na）, silica powder, talc and magnesium stearate] were investigated. The results showed that lactose, mannitol, talc and magnesium stearate existed in a crystalline form, and the others existed in an amorphous form. The effects of tablet compression and stress testing on crystalline stabilities of these excipients were investigated. Furthermore, the influences of physical mixtures of clopidogrel bisulfate and above excipients on crystalline stability of clopidogrel bisulfate were preliminary investigated, and the crystalline changes of clopidogrel bisulfate in the mixtures were tested as well. The results showed that starch, MCC, silicon dioxide, L-HPC, silica powder and talc had good crystalline stability and drug-excipient compatibility. In high humidity test, the PXRD patterns of lactose, mannitol and magnesium stearate had significant changes, while PVP, CMC-Na, CMS-Na and CC-Na were in liquid states due to their high hydroscopicity. The crystalline form of clopidogrel bisulfate was changed in all physical mixtures in high humidity test, indicating the bulk drug was unstable in a high humidity environment.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2016年第8期1034-1038,共5页
Chinese Journal of Pharmaceuticals
关键词
药用辅料
晶型
稳定性
相容性
硫酸氢氯吡格雷
原料药
pharmaceutic excipient
crystalline form
stability
compatibility
clopidogrel bisulfate
bulk drug
