Dissolution from Ethylene Vinyl Acetate Copolymer Long-Acting Implants: Effect of Model Active Ingredient Size and Shape

Abstract

In recent pharmaceutical applications, an active pharmaceutical ingredient (API) can be mixed with a polymer material to yield a composite long-acting drug-delivery device. These devices boast higher patient compliance, localized drug delivery, and lower dosage concentrations, which can increase patient safety. As a laboratory-safe option, calcium carbonate (CaCO3) was used as a drug surrogate to mimic the release kinetics of a low-solubility API. The release of CaCO3 from a poly(ethylene vinyl acetate) (EVA) polymer matrix was studied in ultra-high-purity water. The geometry of CaCO3, along with the manufacturing technique, was manipulated to study the implications on surrogate drug release. It was found that injection molding proved to yield higher burst release, due to higher pressures achievable during manufacturing. The extrusion process can affect the surface concentration of the pharmaceutical ingredient when extruded through a water bath, resulting in a lower initial burst concentration. Regarding CaCO3 geometry, the particle size was more critical than the surface area in terms of CaCO3 release. Larger particles showed a higher release rate, though they also displayed higher variability in release. These data can be used to engineer specific release profiles when designing composite formulations and manufacturing methods for pharmaceutical-drug-delivery applications.

Synthesis of Vinyl Acetate Monomer Over PdCu Alloys: The Role of Surface Oxygenation in the Reaction Path

“…For example, in PVAc synthesis, PVA‐OH can be used as a carrier agent for microfiber, membrane applications, drug delivery systems, and polyketone synthesis. [ 11–15 ] In the past, an hylene, and acetic acid, in an oxidative medium and in the presence of CO 2 . [ 16,17 ] Ethylene acetoxidation is a catalytic reaction that produces VAM through the reaction of C 2 H 4 and CH 3 COOH at low O 2 coverage over Pd surfaces in the gas phase, as described by Equation (1) $$$$\begin{eqnarray} {\rm{C}}{{\rm{H}}_{\rm{2}}}{\rm{ = C}}{{\rm{H}}_{\rm{2}}}{\rm{ + C}}{{\rm{H}}_{\rm{3}}}{\rm{COOH + 0}}{\rm{.5}}{{\rm{O}}_2} \to {\rm{C}}{{\rm{H}}_{\rm{3}}}{\rm{COOCH = C}}{{\rm{H}}_{\rm{2}}}{\rm{ + }}{{\rm{H}}_{\rm{2}}}{\rm{O}}\nonumber\hspace*{-10pt}\\ \end{eqnarray}$$$$…”

“…For example, in PVAc synthesis, PVA-OH can be used as a carrier agent for microfiber, membrane applications, drug delivery systems, and polyketone synthesis. [11][12][13][14][15] In the past, an hylene, and acetic acid, in an oxidative medium and in the presence of CO 2 . [16,17] Ethylene acetoxidation is a catalytic reaction that produces VAM through the reaction of C 2 H 4 and CH 3 COOH at low O 2 coverage over Pd surfaces in the gas phase, as described by Equation ( 1)…”