Enhanced Release of Lidocaine From Supersaturated Solutions of Lidocaine In A Pressure Sensitive Adhesive
Transdermal systems consisting of a pressure sensitive adhesive (PSA) supersaturated with drug were studied with the objective of enhancing drug release. Lidocaine (LC) and Duro-Tak®87-2287 (PSA) were the model components. In vitro release of LC through a composite membrane consisting of multiple layers of cellulose membrane and a silicone membrane was significantly higher from supersaturated LC/PSA systems compared to systems in which drug had crystallized. Drug loading was an important factor influencing the release of LC from the systems. Hydration of the LC/PSA systems may reduce drug release by promoting crystallization of the supersaturated systems. The physical stability of the systems was evaluated kinetically and thermodynamically using thermal analysis and then applying theories of nucleation, e.g., the Fisher-Turnbull equation; and phase transformation, e.g., the Avrami equation. It was found that nucleation rather than the crystal growth process governed crystallization of LC from the supersaturated systems. Nucleation is a diffusion-controlled process, which is dependent on the viscoelastic properties of the PSA medium. Crystallization of LC in the PSA systems had a two-phase temperature dependence with the values of kinetic parameters, such as the Avrami exponent and the Avrami constant, remaining constant over a low temperature range. Over a higher temperature range, however, the crystallization behavior of LC cannot be explained by the conventional Avrami theory, and it was found that a time dependent nucleation rate may account for this behavior. The physical chemical properties of LC/PSA systems were characterized using thermal analysis and FT-IR. The thermodynamic state of the supersaturated systems was evaluated from the composition dependence of the glass transition temperatures, and the LC/PSA interactions were characterized by FT-IR. An intermediate interaction between LC and the PSA was found, resulting in a conformation entropy relaxation of the polymer systems. LC is actively involved in the relaxation of the PSA throughout the composition range. This may contribute to the physical stability of the supersaturated LC/DT2287 systems by reducing the amount of free LC in the systems.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:transdermal drug delivery supersaturation pressure sensitive adhesive lidocaine crystallization kinetics physicalchemical characterization
Date of Publication:01/01/2003