Gwak Hye-Sun, Choi Jun-Shik, Choi Hoo-Kyun
College of Pharmacy, Ewha Women's University, Seoul 120-750, Republic of Korea.
Int J Pharm. 2005 Jun 13;297(1-2):156-61. doi: 10.1016/j.ijpharm.2005.03.016. Epub 2005 Apr 25.
Piroxicam can be ionized as a zwitterion that has two pKa values (pKa1=1.86 and pKa2=5.46). Consequently, piroxicam has a low solubility in both polar and nonpolar media, and a low lipophilicity, which results in a low permeability. Three piroxicam-ethanolamine salts were prepared, which had a higher area under the curve (AUC) than piroxicam. There were minimal differences in the AUC among the salt forms. It was reported that the piroxicam triethanolamine salt had a lower permeability across the skin than piroxicam but it had a higher oral bioavailability. Piroxicam monoethanolamine showed the highest Cmax followed by piroxicam diethanolamine and piroxicam triethanolamine. The dissolution rates of piroxicam and its salts were similar at pH 1.2. Piroxicam monoethanolamine showed the highest dissolution rate at pH 6.8, which was followed by the piroxicam diethanolamine and piroxicam triethanolamine salts. The order of dissolution rate at pH 6.8 matched the order of Cmax or the AUC after oral administration.
吡罗昔康可离子化为两性离子，有两个pKa值（pKa1 = 1.86和pKa2 = 5.46）。因此，吡罗昔康在极性和非极性介质中的溶解度都很低，亲脂性也低，这导致其渗透性较低。制备了三种吡罗昔康 - 乙醇胺盐，它们的曲线下面积（AUC）比吡罗昔康更高。盐形式之间的AUC差异极小。据报道，吡罗昔康三乙醇胺盐经皮渗透性比吡罗昔康低，但口服生物利用度更高。吡罗昔康单乙醇胺的Cmax最高，其次是吡罗昔康二乙醇胺和吡罗昔康三乙醇胺。吡罗昔康及其盐在pH 1.2时的溶解速率相似。吡罗昔康单乙醇胺在pH 6.8时的溶解速率最高，其次是吡罗昔康二乙醇胺盐和吡罗昔康三乙醇胺盐。pH 6.8时的溶解速率顺序与口服给药后的Cmax或AUC顺序一致。
