Institute of Pharma Technology, University of Applied Sciences Northwest, Switzerland, Gründenstrasse 40, Basel, Switzerland.
Swiss Nanoscience Institute, Nano Imaging Lab, University of Basel, Klingelbergstrasse 82, Basel, Switzerland.
Pharm Res. 2018 Feb 21;35(3):69. doi: 10.1007/s11095-017-2300-6.
The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even though such interface effects can be of pharmaceutical relevance. Such potential effects in drug nanosuspensions were to be studied for temperatures of 25 and 37°C by using complementary surface analytical methods.
Atomic force microscopy, inverse gas chromatography and UV surface dissolution imaging were used together for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively.
It was demonstrated that in case of bezafibrate nanosuspension, a surface modification occurred at 37°C compared to 25°C, which notably affected dissolution rate. By contrast, no similar effect was observed in case of fenofibrate nanoparticles.
The combined usage of analytical surface methods provides the basis for a better understanding of phenomena that take place on drug surfaces. Such understanding is of importance for pharmaceutical development to achieve desirable quality attributes of nanosuspensions.
在药物纳米混悬剂的开发中，仍然主要采用反复试验的方法。物理化学分散稳定性是主要关注点，因此通常采用各种分析方法。尽管纳米颗粒表面的变化可能具有药物相关性，但人们显然较少关注这些界面效应。本研究采用互补的表面分析方法，研究了 25 和 37°C 温度下药物纳米混悬剂的潜在表面变化。
首次将原子力显微镜、反气相色谱法和 UV 表面溶解成像法结合用于评估通过湿磨获得的药物纳米混悬剂。选择非诺贝特和苯扎贝特作为模型药物，十二烷基硫酸钠和羟丙基纤维素分别作为阴离子和空间位阻稳定剂。
研究表明，与 25°C 相比，37°C 时，贝扎贝特纳米混悬剂的表面发生了修饰，这显著影响了药物的溶出速率。相比之下，非诺贝特纳米颗粒则没有观察到类似的效果。
分析表面方法的联合使用为更好地理解药物表面发生的现象提供了基础。这种理解对于药物开发实现纳米混悬剂所需的质量属性具有重要意义。
