Drug Release from Poly(dimethylsiloxane)-Based Matrices: Observed and Predicted Stabilization of the Release Rate by Three-Layer Devices

Abstract

Realistic mathematical modeling can greatly facilitate the optimum design of matrix-controlled release (MCR) devices. Here, we present a practical example of a relevant methodology, based on a previously developed model for symmetrical, three-layer MCR devices. The experimental system is based on PDMS matrices incorporating 10% of poly(ethylene glycol) and loaded with theophylline. The matrices were either single-layer devices uniformly loaded with theophylline or symmetrical threelayer devices with a uniformly loaded inner layer and theophylline-free outer layers. The theophylline loads, and the geometrical characteristics of the multilayer matrices, were chosen according to general guidelines for improved uniformity of rate, previously formulated by model calculations. As anticipated, these devices were found to effectively stabilize the rate of release, as compared to the corresponding single-layer system. The main kinetic characteristics of the experimental systems were then successfully reproduced theoretically by a set of input parameters (pertaining to the transport properties of the polymer−solute−solvent system), derived mainly from the release experiments in monolithic matrices. Finally, the same input parameters were used for exploring theoretically the range of the three-layer device parameters that are expected to preserve the observed improved performance of the experimental systems.

Silicone Surface with Drug Nanodepots for Medical Devices

“…Installing a drug-release character to any PDMS materials has also been carried out by directly dispersing drug molecules into a polymeric matrix. 20,21 Nevertheless, this direct mixing method is only popular in pharmaceutical preparations and devices, such as a silicone elastomer vaginal gel with antiviral activity, 22 intravaginal drug-delivery rings, 23−25 and transdermal drug-delivery patches, 26 in which the mechanical properties and long-term stability of the devices are not critical. To conserve the mechanical and viscoelastic properties of PDMS medical devices, only limited amounts of drugs could be mixed into the polymeric matrix; thus, the release of sufficient amounts of drugs could not be attained through this strategy.…”

“…Covalent linking of drug molecules to the surface is another approach to lessen the infection, inflammation, and tissue reaction levels. − However, in addition to a low drug content on the surface, another limitation of this approach is that the tethered drug moieties are fixed at the device’s surface and can neither migrate into nor build up to a high drug concentration in the surrounding tissue despite the fact that a high drug concentration during the critical postimplantation period is required for better improvement of the postimplantation reaction. , Moreover, this approach requires different drugs to be individually customized onto the surface of the devices. Installing a drug-release character to any PDMS materials has also been carried out by directly dispersing drug molecules into a polymeric matrix. , Nevertheless, this direct mixing method is only popular in pharmaceutical preparations and devices, such as a silicone elastomer vaginal gel with antiviral activity, intravaginal drug-delivery rings, − and transdermal drug-delivery patches, in which the mechanical properties and long-term stability of the devices are not critical. To conserve the mechanical and viscoelastic properties of PDMS medical devices, only limited amounts of drugs could be mixed into the polymeric matrix; thus, the release of sufficient amounts of drugs could not be attained through this strategy …”