School of Veterinary Science, The University of Queensland, Gatton QLD 4343, Australia.
Vet J. 2013 Jun;196(3):456-60. doi: 10.1016/j.tvjl.2012.11.004. Epub 2013 Jan 12.
This study investigated the effects of formulation on the penetration and retention kinetics of budesonide through canine skin in vitro. Full thickness, thoracic, dog skin was mounted in Franz-type diffusion cells and randomly assigned to receive one of three 0.025% (0.25mg/mL) budesonide-containing formulations: Barazone (BZ, a novel formulation), isopropyl myristate (IPM) or propylene glycol (PG). At regular intervals over 84h, the amount of budesonide penetrating or retained within the skin was quantified using high performance liquid chromatography. The restricted (or residual) maximum likelihood mixed model predicted that the flux of budesonide from BZ was 9.2-fold (P<0.001) and 105-fold (P<0.001) greater than from IPM and PG, respectively. Similarly, the skin retention of budesonide from BZ was more than 3-fold (P<0.0001) and nearly 6-fold (P<0.0001) greater than from IPM and PG, respectively. This study has demonstrated that the formulation can greatly affect the skin penetration and retention of budesonide in dogs, and consequently could be selected to maximise drug concentration and retention at the site of action. This has the potential to improve the efficacy and safety of, and owner compliance with, topical glucocorticoid therapy in dogs.
本研究考察了制剂对犬体外皮肤中布地奈德渗透和滞留动力学的影响。全厚，胸，狗皮被安装在 Franz 型扩散细胞中，并随机分配接受三种 0.025%（0.25mg/mL）布地奈德含制剂之一：Barazone（BZ，一种新型制剂）、肉豆蔻异丙酯（IPM）或丙二醇（PG）。在 84 小时的定期间隔内，使用高效液相色谱法定量测定穿透或保留在皮肤内的布地奈德量。受限（或剩余）最大似然混合模型预测，BZ 中布地奈德的通量分别比 IPM 和 PG 高 9.2 倍（P<0.001）和 105 倍（P<0.001）。同样，BZ 中布地奈德的皮肤保留量分别比 IPM 和 PG 高 3 倍以上（P<0.0001）和近 6 倍（P<0.0001）。这项研究表明，制剂可以极大地影响布地奈德在狗皮肤中的渗透和滞留，因此可以选择制剂来最大限度地提高作用部位的药物浓度和滞留。这有可能提高狗用局部糖皮质激素治疗的疗效、安全性和主人的依从性。
