Elezović Alisa, Marić Amina, Biščević Amila, Hadžiabdić Jasmina, Škrbo Selma, Špirtović-Halilović Selma, Rahić Ognjenka, Vranić Edina, Elezović Amar
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina.
Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo.
ADMET DMPK. 2020 Dec 9;9(1):57-68. doi: 10.5599/admet.916. eCollection 2021.
The kinetics of passive transport of ketoprofen and metformin, as model substances for high and low permeability, respectively, across the artificial membrane under the influence of the pH of donor solution was investigated. There was an upward trend in the apparent permeation coefficient ( ) of ketoprofen with the decrease in pH to a value close to pa. At the pH value below pa the permeation coefficient had lower value, due to the higher retention of ketoprofen in the artificial membrane. Metformin is a low permeable compound, and the highest permeation values were recorded at pH 7.4. Two dissociation constants determine that metformin at physiological pH exists as a hydrophilic cationic molecule, i.e. predominantly in ionized form. At pH values below 2.8, metformin mainly exists in diprotonated form, and it was, thus, very poorly permeable. The highest retention, i.e. affinity of both ketoprofen and metformin to the membrane, was at the lowest pH values, which is explained by different mechanisms. At higher pH values of donor compartment the substances showed significantly less affinity to the membrane. The obtained values of apparent permeation coefficients at studied pH values showed good correlation with the obtained experimental values by other in vitro methods.
分别以酮洛芬和二甲双胍作为高渗透性和低渗透性的模型物质，研究了供体溶液pH值对其在人工膜上被动转运动力学的影响。随着pH值降低至接近pa的值，酮洛芬的表观渗透系数（ ）呈上升趋势。在pH值低于pa时，由于酮洛芬在人工膜中的保留率较高，渗透系数较低。二甲双胍是一种低渗透性化合物，在pH 7.4时记录到最高的渗透值。两个解离常数决定了二甲双胍在生理pH下以亲水性阳离子分子形式存在，即主要以离子化形式存在。在pH值低于2.8时，二甲双胍主要以双质子化形式存在，因此其渗透性很差。酮洛芬和二甲双胍对膜的保留率最高，即亲和力最高，出现在最低pH值时，这是由不同机制解释的。在供体隔室较高的pH值下，这些物质对膜的亲和力明显较低。在研究的pH值下获得的表观渗透系数值与通过其他体外方法获得的实验值显示出良好的相关性。
