Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Ave., Brooklyn, NY 11201, USA.
Drug Dev Ind Pharm. 2011 May;37(5):613-7. doi: 10.3109/03639045.2010.534098.
This study was designed to quantify the effects of penetration enhancers on systemic bioavailability of 0.3% meloxicam (MLX) hydroxypropylcellulose gels. Cutaneous microdialysis was also performed to assess dermis availability and to better understand the penetration process. The gels tested were a 1% oleic acid gel, a 5% menthol gel, and a control gel without penetration enhancers.
To assess systemic bioavailability, three female rabbits received according to a crossover design 0.135 g/cm(2) of gel applied to a 7.5 × 7.5 cm area of their shaved back and a short (5 min) infusion of 1 mg. In each experiment, blood samples were collected serially for 36 h and analyzed by a validated HPLC method. For skin bioavailability studies, 0.135 g/cm(2) of the same gels were applied to a 1 × 2 cm area on top of a microdialysis probe previously inserted in the dermis. Dialysate samples were collected for 6 h every 30 min.
Systemically, the 5% menthol gel delivered 3.93 ± 0.85 mg of MLX versus the 1.41 ± 0.24 mg of the oleic acid gel. Only traces of MLX were detectable from the control gel. In dermis, substantial concentrations of MLX were detected only after the application of the menthol gel, whereas skin concentration from the control gel and the 1% oleic acid gel were always below the lowest limit of quantification (LLOQ).
The 5% menthol gel can possibly deliver therapeutically relevant amount of MLX in vivo. Dermis concentrations can be predictive of systemic plasma levels.
本研究旨在量化渗透增强剂对 0.3%美洛昔康（MLX）羟丙基纤维素凝胶系统生物利用度的影响。还进行了皮肤微透析，以评估真皮的可用性，并更好地了解渗透过程。测试的凝胶分别为 1%油酸凝胶、5%薄荷醇凝胶和不含渗透增强剂的对照凝胶。
为了评估系统生物利用度，三只雌性兔子根据交叉设计接受了 0.135 g/cm(2)的凝胶，涂抹在其剃光的背部 7.5×7.5 cm 区域，并进行了 5 分钟的 1 毫克短输注。在每个实验中，连续采集血液样本 36 小时，并通过验证的 HPLC 方法进行分析。对于皮肤生物利用度研究，将相同的凝胶 0.135 g/cm(2)应用于先前插入真皮的微透析探针的 1×2 cm 区域。每隔 30 分钟收集 6 小时的透析液样本。
在系统中，5%薄荷醇凝胶输送 3.93±0.85 mg MLX，而油酸凝胶输送 1.41±0.24 mg。对照凝胶中仅检测到痕量的 MLX。在真皮中，仅在应用薄荷醇凝胶后才检测到大量的 MLX，而对照凝胶和 1%油酸凝胶的皮肤浓度始终低于最低定量限 (LLOQ)。
5%薄荷醇凝胶可能能够在体内输送治疗相关量的 MLX。真皮浓度可预测系统血浆水平。
