Implantable Drug Delivery Systems: experimental validation of a mathematical model applicable to cylindrical geometry

JUAN C. D. IBARRA; IGNACIO M. HELBLING; JULIO A. LUNA

Beijing

Simposio; 5th Annual World Symposium of Drug Delivery System; 2015

Amechanistic model applicable to release profile from cylindrical Implantable DrugDelivery System (IDDS) was developed in previous study. This model allows theintroduction the volume of the release medium where the drug is delivered, as aparameter. Thus, sink conditions assumption for the release test can be avoided.The design of the IDDS is generally of cylindrical geometry because of theimplantation of the devices is performed with the use of needles. Thevalidation of this mathematical model was performed using the drug releaseprofiles obtained from in vitro release testing and the results are shown inthis paper. EVA cylinders loaded with progesterone as a model drug werefabricated by hot melt extrusion. The incorporation of progesterone in thepolymer was achieved by impregnation process. The values of the parametersrequired for using the mathematical model were determined by own experiments.The values of maximum solubility of progesterone in the release medium and in theEVA polymer were determined. The partition coefficient values were calculatedusing the solubility values obtained. The diffusion coefficient of progesteroneEVA was determined with assays from Franz diffusion cell. In vitro releasetests were carried out varying three variables. Initial drug loading, theexternal diameter of the cylindrical matrix and the volume of the releasemedium were tested. The method of comparison in pairs as statistical analysistechnique was used. A comparison between experimental data of release andtheoretical predictions of mathematical model was performed. f1and f2 factors were used in order to measure quantitativelythe fit of the theoretical prediction to the experimental data. Excellentagreement between theoretical and experimental data profiles for the threevariables analyzed was observed. In the release medium used (ethanol 20% v/v) Fickiandiffusion through the matrix was the controlling mechanism of release. Inconclusion, the mathematical model can be considered as a reliable tool for thedesign and optimization of in vitro release profiles for cylindrical matrices.