Effect of wet milling process on the solid state of indomethacin and simvastatin.
Effect of wet milling process on the solid state of indomethacin and simvastatin.
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DOI：
10.1016/j.ijpharm.2009.06.029
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发表时间：
2009-10
影响因子：
5.8
通讯作者：
Puneet Sharma;W. Denny;S. Garg
中科院分区：
文献类型：
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作者：
Puneet Sharma;W. Denny;S. Garg
本研究的目的是研究湿法球磨对吲哚美辛(IMC)和辛伐他汀(SIM)固体状态的影响。采用高压均质(HPH)进行湿法球磨。采用聚乙烯吡咯烷酮K25(PVP)和泊洛沙姆407(P407)作为悬浮稳定剂。采用粒度分析仪、扫描电子显微镜(SEM)、红外光谱(IR)和调制温度差示扫描量热仪(MTDSC)对湿磨前后的样品进行了表征。湿法球磨后，IMC的表面形貌和红外光谱显示表面非晶化，而SIM的固态未受影响。MTDSC不能检测到IMC中的表面非晶化，这表明如果存在表面非晶化，它只在很低的水平上。这些结果与以前的报道相反，以前的报道中，IMC和SIM的干磨导致了晶体颗粒的非晶化。此外，在没有水的情况下，IMC的冷冻粉碎产生了非晶态，而在相同的冷冻粉碎条件下，水的存在导致了类似于湿法粉碎后的固态。这些结果表明，水在晶体药物湿法研磨过程中起到了抑制非晶化的作用。
The aim of this study was to investigate the effect of wet milling on the solid state of indomethacin (IMC) and simvastatin (SIM). Wet milling was performed using high pressure homogenization (HPH). Polyvinylpyrrolidone-K25 (PVP) and poloxamer 407 (P407) were used as suspension stabilizers. Samples were characterized before and after wet milling using particle size analyzer, scanning electron microscopy (SEM), infrared (IR) spectroscopy and modulated temperature differential scanning calorimetry (MTDSC) techniques. After wet milling of IMC, physical appearance and IR spectra indicated surface amorphization; however, the solid state of SIM remained unaffected. MTDSC could not detect surface amorphization in IMC, suggesting that if present, it was only at very low levels. These results are in contradiction to the previous reports where dry milling of IMC and SIM resulted in amorphization of crystalline particles. Moreover, cryogrinding of IMC in the absence of water resulted in an amorphous form while presence of water using the same cryogrinding conditions resulted in a solid state similar to that obtained after wet milling. These results signify the role of water in inhibiting the amorphization during wet milling of crystalline drugs.