Medicines Department, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Drug Dev Ind Pharm. 2013 Jul;39(7):1098-106. doi: 10.3109/03639045.2012.711833. Epub 2012 Aug 20.
Nifedipine (NFD) has been used for the treatment of cutaneous lesions caused by peripheral vascular disease and diabetic ulcers. NFD was formulated at 8% in three semi-solid formulations: Polaxamer 407 Lecithin Organogel (PLO), PLO plus Transcutol(®), and an oil-in-water (o/w) emulsion. In vitro release and permeation tests were carried out using a synthetic (cellulose acetate) or natural membrane (pig ear skin), respectively, mounted in a Franz-type diffusion cell at 37°C in a constant water bath. As a receptor solution, isotonic phosphate buffer at pH 7.4 was used. All samples were analyzed by high-performance liquid chromatography by employing a previously validated method. The drug flow values were 6.126 ± 0.288, 4.030 ± 0.081, and 6.660 ± 0.254 μg/cm(2)/h for PLO, PLO plus Transcutol(®), and o/w emulsion, respectively. The three formulations did not show significant differences in drug flow, considering p > 0.05. Furthermore, their penetration profiles in both the epidermis and dermis were statistically different. Thus, the incorporation of NFD in PLO, PLO plus Transcutol(®), and o/w emulsion changed the drug thermodynamic activity, as expected. In addition, Transcutol(®) increased the solubility of NFD in the formulation and promoted its penetration in both the epidermis and dermis.
硝苯地平(NFD)已被用于治疗外周血管疾病和糖尿病溃疡引起的皮肤损伤。NFD 以 8%的浓度被制成三种半固体制剂:泊洛沙姆 407 卵磷脂组织凝胶(PLO)、PLO 加 Transcutol®和水包油(o/w)乳剂。体外释放和渗透试验分别使用合成(醋酸纤维素)或天然膜(猪耳皮)进行,在 37°C 的恒温水浴中安装在 Franz 型扩散池中。作为受体溶液,使用等渗磷酸盐缓冲液 pH7.4。所有样品均通过高效液相色谱法进行分析,采用先前验证的方法。PLO、PLO 加 Transcutol®和 o/w 乳剂的药物流量值分别为 6.126 ± 0.288、4.030 ± 0.081 和 6.660 ± 0.254 μg/cm 2 /h。考虑到 p > 0.05,三种制剂的药物流量没有显著差异。此外,它们在表皮和真皮中的渗透分布在统计学上也不同。因此,正如预期的那样,将 NFD 掺入 PLO、PLO 加 Transcutol®和 o/w 乳剂中改变了药物的热力学活性。此外,Transcutol®增加了制剂中 NFD 的溶解度,并促进了其在表皮和真皮中的渗透。