Deutsch-Französischer Diskurs: Vortrag von Prof. Dr. Thierry Vandamme

Pharmacological forms which take into account individual absorbtion, distribution, methabolism and excerction (ADME) rates of a patient constitute an active field of pharmacological research. Recently we have proposed an approach allowing to regulate the lag time and the rate of the release of an active pharmaceutical ingredient (API) from oral dosages [1]. The approach consists in rolling up a biopolymer stripe carrying the API reservoirs in form of a cylindrical capsule. Rolling transforms the lateral distribution of the API in the radial one, which determines the release kinetics. The approach is illustrated by gelatin gastroretentive oral dosages for controlled release of riboflavin and propranolol. The dosages, which have the form of tight scrolls, are stabilized against unrolling by Transglutaminase-mediated crosslinking of the consecutive layers. The scrolls swell in the release media, Fasted State Simulated Gastric Fluid (FaSSGF), to the dimensions which exceed the average diameter of the human pyloric sphincter, but remain mechanically robust to resist the stomach peristaltic contractions during at least 24 hours, sufficient for the drug release. Eventually the scrolls are degraded by the release media and can be evacuated from the stomach.

Another approach which we explore for the control of the APIs release kinetics consists in formation of the diffusion barriers with tuned characteristics. This approach might be especially useful for the design of transdermal patches for the delivery of high potency APIs.  In our method [2], the diffusion barrier layer is formed by irradiating poly(dimethylsiloxane) (PDMS) with a mid-infrared (10.6mm) CO₂ laser. This process directly creates a diffusion barrier layer on the PDMS surface by forming heavily crosslinked network in the polymer matrix. The optimal irradiation conditions were investigated by modulating the defocusing distance, laser power, and number of scanning passes. The barrier thickness can reach up to 70 µm as observed by scanning electron microscope (SEM). The attenuated total reflectance (ATR), electron dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS) analyses collectively confirmed the formation of the SiO_x structure on the modified surface, based on the decreased methyl group signal, and the increased oxygen/silicon ratio. The diffusion test with the model drugs (Rhodamine B and Donepezil) demonstrated that the modified surface exhibits effective diffusion barrier properties and that the rate of drug diffusion through the modified barrier layer can be controlled by optimization of the irradiation parameters.