Department of Pharmaceutics, Biopoharmaceutics and NutriCosmetics, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
Int J Pharm. 2010 May 31;391(1-2):322-9. doi: 10.1016/j.ijpharm.2010.03.002. Epub 2010 Mar 7.
PX-18 is a new highly potent phospholipase A(2) inhibitor with a poor aqueous solubility. Therefore, it was formulated as nanosuspensions with an active content of 1% (w/w), 5% (w/w) and 10% (w/w) using high-pressure homogenization. By contact angle measurements on compressed discs of PX-18, Tween 80 was identified as best wetting agent of PX-18 and therefore used to stabilize the nanosuspensions. The achieved particle size of all nanosuspensions was well in the nanometer range. For the 1% (w/w) PX-18 nanosuspension an average particle size below 50 nm was measured by photon correlation spectroscopy (PCS). A good reproducibility of the mean particle size was found in between different batches. As postulated by the zeta potential of the nanosuspensions, a good physical stability over an observation period of 180 days was obtained when stored at 5+/-3 degrees C. PX-18 formulated as nanosuspensions was chemically stabile. An increase in saturation solubility was found after formulating PX-18 as nanosuspension compared to bulk material, favourable for increasing bioavailability.
PX-18 是一种新型的高活性的、水溶性差的磷脂酶 A2 抑制剂。因此，它被制成了纳米混悬剂，其中活性成分的含量分别为 1%（w/w）、5%（w/w）和 10%（w/w），采用高压匀质法制备。通过对 PX-18 压缩盘的接触角测量，确定吐温 80 是 PX-18 的最佳润湿剂，并将其用于稳定纳米混悬剂。所有纳米混悬剂的粒径都很好地处于纳米范围内。对于 1%（w/w）的 PX-18 纳米混悬剂，通过光子相关光谱（PCS）测量得到的平均粒径小于 50nm。在不同批次之间发现了很好的平均粒径重现性。正如纳米混悬剂的zeta 电位所假设的那样，当在 5+/-3 摄氏度下储存时，纳米混悬剂在 180 天的观察期内具有良好的物理稳定性。以纳米混悬剂形式制备的 PX-18 在化学上是稳定的。与原料药相比，将 PX-18 制成纳米混悬剂后发现其饱和溶解度增加，有利于提高生物利用度。
