Jin Nan, Pyo Sung Min, Keck C M, Müller R H
Pharmazie. 2019 May 1;74(5):277-285. doi: 10.1691/ph.2019.8169.
Azithromycin was optimized as nanocrystals with a drug content of 10.0 % (w/w) and a surfactant D- -tocopheryl polyethylenglycol 1000 succinate (TPGS) content of 1.0 % (w/w) using bead milling for 10 min. The photon correlation spectroscopy (PCS) diameter of the bulk population was 189 nm, laser diffraction (LD) diameter 90 % was 370 nm. Spherical morphology of the optimal nanocrystals was observed by transmission electron microscope (TEM). They were stable over 1 year of storage at 4 °C with the particle size within the nanometer range which was confirmed by PCS, LD and light microscope. An acceptable physical stability of 2 years was also obtained when stored at 4 °C. No microbial attack to the nanocrystals was observed before 3 years storage at 4 °C. The saturation solubility of the nanocrystals was up to triple compared to the raw drug powder (RDP) in water. When incorporated into the gel base, highest penetration efficacy was achieved by the optimal nanocrystals compared to 1) the clinically effective ethanol-solution-gel, 2) the gel with propylene glycol and 3) the gel with RDP in the porcine ear penetration study. Even though propylene glycol improved saturation solubility of nanocrystals, it could not bring benefit to nanocrystals in the penetration study. Based on these optimized azithromycin nanocrystals, topical administration for enhanced dermal bioavailability of azithromycin seems to be feasible.
采用珠磨法10分钟，将阿奇霉素优化为药物含量为10.0%（w/w）、表面活性剂琥珀酸聚乙二醇1000维生素E（TPGS）含量为1.0%（w/w）的纳米晶体。总体群体的光子相关光谱（PCS）直径为189nm，激光衍射（LD）直径90%为370nm。通过透射电子显微镜（TEM）观察到最佳纳米晶体的球形形态。它们在4℃储存1年以上稳定，粒径在纳米范围内，这通过PCS、LD和光学显微镜得到证实。在4℃储存时也获得了2年的可接受物理稳定性。在4℃储存3年之前未观察到纳米晶体有微生物侵袭。纳米晶体在水中的饱和溶解度比原料药粉末（RDP）高达三倍。在猪耳渗透研究中，与1）临床有效的乙醇溶液凝胶、2）含丙二醇的凝胶和3）含RDP的凝胶相比，最佳纳米晶体掺入凝胶基质后实现了最高的渗透效果。尽管丙二醇提高了纳米晶体的饱和溶解度，但在渗透研究中它并不能给纳米晶体带来益处。基于这些优化的阿奇霉素纳米晶体，局部给药以提高阿奇霉素的皮肤生物利用度似乎是可行的。
