Solubility, thermodynamic activity and drug flux out of solid polymer films through membranes

首次从根本上研究了载药固体聚合物膜的释放/渗透过程中通量、热力学活性和分配系数之间的关系。在该项目的前2年，建立了一种方法来测定药物在薄固体聚合物膜中的饱和溶解度，并公布了结果（申请的目的1）。在接下来的2年中，将处理该项目的目标2，即定量测定释放/渗透与热力学活性之间的关系，即聚合物膜中药物的饱和度。对于所选的3种不同亲脂性的药物，将制备不同压敏粘合剂的载药薄膜。它们具有不同的饱和溶解度，因此对于给定的热力学活性值，可以具有不同的药物浓度。通过向聚合物膜中加入抗溶解剂来调节饱和溶解度。将测定药物从这些膜通过切除的皮肤膜或人工膜的释放/渗透。根据这些结果，将确定通量、热力学活性和浓度之间的关系。此外，我们将继续并完成对药物在膜或角质层脂质相中的饱和溶解度的研究。通过所有这些数据，我们希望回答这个问题，最大测量通量是否部分受到膜中药物饱和溶解度的限制。前2年的工作现在使我们有可能为我们现在作出贡献，以更好地理解在多层的扩散过程的理论，包括一个聚合物薄膜和膜。

For release/permeation processes from drug-loaded solid polymer films, the relationship between flux, thermodynamic activity and partition coefficient is studied fundamentally for the first time . In the first 2 years of the project a method was established to determine the saturation solubility of a drug in a thin, solid polymer film and the results published (objective 1 of the application). In the coming 2 years the object 2 of the project will be handled, namely a quantitative determination of the relationship between release/permeation and thermodynamic activity, ie the degree of saturation of the drug in the polymer film. For 3 selected drugs of different lipophilicity drug-laden thin films of different pressure-sensitive adhesives will be prepared. These have different saturation solubility and can therefore for a given value of thermodynamic activity have different drug concentrations. The saturation solubility is adjusted by the addition of anti-dissolving agents to the polymer film. The release/permeation of the drug from these films through excised skin membranes or artificial membranes will be determined. From these results the relationship between flux, thermodynamic activity and concentration will be determined. In addition, our studies of the saturation solubility of drugs in membranes or in a stratum corneum lipid phase will be continued and completed. With all these data we hope to answer the question, whether the maximum measured flux is partially limited by the saturation solubility of the drug in the membrane. The work of first 2 years now makes it possible for us now to contribute to a better theoretical understanding of diffusion processes in multi-layers, consisting of a polymer film and the membrane.