Controlling Indomethacin Release through Vapor-Phase Deposited Hydrogel Films by Adjusting the Cross-linker Density

Abstract

Vapor-phase deposited polymer coatings are applied on thin indomethacin films to modify the drug release. Hydrogel-forming co-polymers of 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate were prepared directly on top of solution cast indomethacin thin films by initiated Chemical Vapor Deposition (iCVD). This technique allows for solvent-free processing under mild conditions, thus minimizing a potential impact on the pharmaceutical. The drug release behavior, among other properties, was evaluated for polymers of different compositions and at different temperatures. The data show that the release kinetics can be tuned by several orders of magnitude as the cross-linker fraction is varied in the polymer coating. While uncoated indomethacin films were fully released within an hour, polymer coatings showed gradual liberation over several hours to days. Additional insight is gained from evaluating the experimental dissolution data in the framework of diffusive transport. The results of this study show that the iCVD technique has some promises for pharmaceutical technology, potentially allowing for tailored release behavior also for other drug systems.

Initiated Chemical Vapor Deposition of Crosslinked Organic Coatings for Controlling Gentamicin Delivery

“…The release constant, k er , decreases from the uncoated sample to the coated ones and among those, the one with the 85% EGDMA shows the lowest release constant. The values for the release constants obtained in this study are in agreement with the release constants obtained by previous studies based on similar crosslinked hydrogels [21].…”

“…Polymers containing less than 29% of EGDMA dissolved in water. The amount of crosslinker leads to changes in the mesh size (i.e., the distance between two consecutive crosslinks) of the polymers and this in turn affects the diffusivity of the water in/out of the layer [21]. In particular, a higher amount of crosslinker leads to a smaller mesh and less swelling, as it can be seen in Figure 2.…”

“…iCVD layers were deposited using a custom-built setup, as described in ref. 21. Substrates were placed in a cylindrical vacuum chamber, on a stage thermoregulated at 30 • C by a water recirculating chiller.…”

“…More details on the release mechanism can be understood by the mathematical models applicable to the release data. Previously, good fits were obtained by applying the diffusion model based on reservoir systems, in which the drug is encapsulated by an outer membrane and gradually released [21,23].…”

“…In both cases, the drug release was pH dependent: at low pH the cross-linked film acted as diffusion barrier, while at neutral pH the film allowed the free diffusion of the drug out of the encapsulant. The crosslinker density in the polymer coating allowed to tune the release kinetics of several orders of magnitude, from hours to days [21]. In another study, McInnes et al [22] reported the iCVD deposition of a temperature-responsive polymeric coating of poly(N-isopropylacrylamide-co-diethylene glycol divinyl ether) (pNIPAM-co-DEGDVE) onto porous silicon loaded with an anticancer drug.…”