Al-Saidan S M
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, SAFAT 13110, Kuwait.
J Control Release. 2004 Nov 24;100(2):199-209. doi: 10.1016/j.jconrel.2004.08.011.
The objective of this study was to prepare saturated solutions of ibuprofen, of different concentrations, and to investigate their effect on permeation of ibuprofen across rat epidermis. Ibuprofen saturated solutions were prepared using 0.1, 0.2, 0.3 and 0.4 M disodium hydrogen phosphate solution (DHP). The solubility of ibuprofen in DHP increased as the molarity of DHP increased. Thus the four saturated solutions of ibuprofen (0.1M-DHP-IBU, 0.2M-DHP-IBU, 0.3M-DHP-IBU and 0.4M-DHP-IBU) have different concentrations of the same drug, and showed same pH (pH 7.0+/-1). The permeability study was also carried out using human epidermis and silastic membrane. Permeation rate of ibuprofen across rat epidermis and human epidermis from 0.4M-DHP-IBU was much greater than from 0.1M-DHP-IBU. The magnitudes of increase in the drug flux were 46.4-fold with rat epidermis and 9.4-fold with human epidermis. Such a great increase in drug flux was not observed with silastic membrane, only 1.4-fold. This suggests that the increased drug flux is likely due to drug-skin interaction and not the increased concentration of ibuprofen per se. Surface tension (ST) measurements of DHP versus ibuprofen concentration showed ST reduction of DHP, from 72 to 27.9 dyn/cm. This is an indication that ibuprofen acted as ionic surfactant and the observed skin permeability enhancement is attributed to disruption of stratum corneum barrier. Results of DSC study supported this assumption. DSC of untreated rat stratum corneum samples showed lipid transitions at 41.9+/-0.0 degrees C (T1), 55.1+/-1.6 degrees C (T(x)), 70.2+/-0.1 degrees C (T2) and 77.5+/-0.1 degrees C (T3), while those pretreated with 0.4M-DHP-IBU did not show the first three lipid transitions. Also, pretreatment of rat epidermis with 0.4M-DHP-IBU enhanced permeation of diclofenac sodium greater than 1250-fold. This corroborates that ibuprofen not only enhances its own permeation but also that of other drugs, such as diclofenac sodium.
本研究的目的是制备不同浓度的布洛芬饱和溶液，并研究它们对布洛芬透过大鼠表皮渗透的影响。使用0.1、0.2、0.3和0.4M磷酸氢二钠溶液（DHP）制备布洛芬饱和溶液。布洛芬在DHP中的溶解度随DHP摩尔浓度的增加而增加。因此，四种布洛芬饱和溶液（0.1M-DHP-IBU、0.2M-DHP-IBU、0.3M-DHP-IBU和0.4M-DHP-IBU）具有相同药物的不同浓度，并显示相同的pH值（pH 7.0±1）。还使用人表皮和硅橡胶膜进行了渗透研究。布洛芬从0.4M-DHP-IBU透过大鼠表皮和人表皮的渗透率远高于从0.1M-DHP-IBU的渗透率。药物通量增加的幅度在大鼠表皮中为46.4倍，在人表皮中为9.4倍。在硅橡胶膜中未观察到如此大的药物通量增加，仅为1.4倍。这表明药物通量的增加可能是由于药物与皮肤的相互作用，而不是布洛芬本身浓度的增加。DHP与布洛芬浓度的表面张力（ST）测量显示DHP的表面张力从7 dyn/cm降低到27.9 dyn/cm。这表明布洛芬起到了离子表面活性剂的作用，观察到的皮肤渗透性增强归因于角质层屏障的破坏。差示扫描量热法（DSC）研究结果支持了这一假设。未处理的大鼠角质层样品的DSC显示在41.9±0.0℃（T1）、55.1±1.6℃（T(x)）、70.2±0.1℃（T2）和77.5±0.1℃（T3）有脂质转变，而用0.4M-DHP-IBU预处理的样品未显示前三个脂质转变。此外，用0.4M-DHP-IBU预处理大鼠表皮可使双氯芬酸钠的渗透率提高超过1250倍。这证实了布洛芬不仅能增强其自身的渗透性，还能增强其他药物如双氯芬酸钠的渗透性。
