Zgoda Marian Mikołaj, Kołodziejska Justyna, Nachajski Michał Jakub
Department of Drug Form Technology, Applied Pharmacy Faculty, Medical University in Lodz.
Polim Med. 2007;37(1):3-24.
The aim of the carried out investigations was to establish relation between rheological parameters of market hydrogels containing ibuprofen and therapeutic agent diffusion coefficient dependent on their prescription. An attempt was made to estimate rheological parameters (structural viscosity, kinetics of volatile components loss) effect on pharmaceutical availability Q and the order of the process of mass exchange through artificial and natural phase boundary. Designed for skin anti-inflammatory hydrogels containing ibuprofen in the form of hydrotropic adduct with lysine (Ibufen, Dolofast), in the form of sodium salt (Nurofen) and in the form of molecular fragmentation of acidic form (Dolgit) were tested. The rate of volatile components loss was estimated with gravimetric method, viscosity measurements of therapeutic agents aqueous solutions were performed with Ubbelohde viscosimeter, while hydrogels rheological parameters - with cone-plate digital rheometer. The rate of ibuprofen penetration through phase boundary (Viscing dialysis membrane and pig perimastoid dermis) into dialysis fluid was determined in vitro. The kinetics of this process was monitored by measuring electric conduction Deltalambda = f(t) of model dialysis fluid. Viscometric measurements of aqueous solutions of ibuprofen lysine salt and ibuprofen sodium salt, by determining boundary viscosity gradient GLL(eta) and calculation of hydrodynamic radius Robs, enabled the applicative solution of Einstein-Smoluchowski equation (D = kT/6Pi r eta) and the estimation of structural value of therapeutic agent diffusion coefficient. Tracing the dependence between diffusion coefficient and shear rate enabled to recognize the preferences of preparations to the process of mass exchange on the phase boundary. An association was confirmed between the determined and calculated rheological parameters and the process of mass exchange on phase boundary through selected dialysis membranes. Mass exchange on phase boundary was found to be the derivative of the process of diffusion and its quantitative aspect depends on the kind of the applied membrane (it is the function of the quantity of statistically distributed pores on the unit of its surface [cm2]). Ibuprofen penetration through an artificial and natural phase boundary is complex. Its mechanism is between the kinetics of "0" and "II" order. The quantitative differentiation of the process of mass exchange between hydrotropic ibuprofen forms: ibuprofen lysine salt > ibuprofen sodium salt > ibuprofen in the form of acid molecule results from the carried out experimental study.
开展这些研究的目的是确定含布洛芬的市售水凝胶的流变学参数与取决于其配方的治疗剂扩散系数之间的关系。尝试评估流变学参数(结构粘度、挥发性成分损失动力学)对药物可用性Q以及通过人工和天然相界面的质量交换过程的级数的影响。对设计用于皮肤抗炎的水凝胶进行了测试,这些水凝胶中的布洛芬分别为与赖氨酸的水溶助长加合物形式(布洛芬赖氨酸盐、多洛芬)、钠盐形式(布洛芬)和酸性形式的分子碎片形式(多吉特)。挥发性成分的损失速率用重量法估算,治疗剂水溶液的粘度用乌氏粘度计测量,而水凝胶的流变学参数用锥板数字流变仪测量。体外测定了布洛芬穿过相界面(聚氯乙烯透析膜和猪乳突周围真皮)进入透析液的速率。通过测量模型透析液的电导率Δλ = f(t)来监测该过程的动力学。通过测定布洛芬赖氨酸盐和布洛芬钠盐水溶液的粘度,确定边界粘度梯度GLL(η)并计算流体动力学半径Robs,从而能够应用爱因斯坦 - 斯莫卢霍夫斯基方程(D = kT/6πrη)并估算治疗剂扩散系数的结构值。追踪扩散系数与剪切速率之间的依赖性能够识别制剂在相界面上质量交换过程中的偏好。确定的和计算出的流变学参数与通过选定透析膜在相界面上的质量交换过程之间的关联得到了证实。发现相界面上的质量交换是扩散过程的导数,其定量方面取决于所用膜的种类(它是其单位表面[cm²]上统计分布的孔数量的函数)。布洛芬穿过人工和天然相界面的过程很复杂。其机制介于“0”级和“II”级动力学之间。水溶助长型布洛芬形式之间质量交换过程的定量差异:布洛芬赖氨酸盐>布洛芬钠盐>酸性分子形式的布洛芬,这是由所进行的实验研究得出的。