Drug Release from Polymer Thin Films and Gel Pellets: Insights from Programmed Microplate Electroanalysis.

Robotic electroanalysis in 24-well microplates was used to determine Paracetamol (PCT) release from thin films of chitosan and two pH-sensitive synthetic polymers as well as blends of the polymers with each other and with agarose. Square-wave voltammograms were recorded automatically in a potential window of 0.35 V-0.85 V vs. Ag/AgCl/0.1 M KCl and their evaluation revealed time-dependent PCT release into acidic and basic media. Comparison of the release profiles showed that pure chitosan layers released PCT quickly in a single-phase process while liberation from synthetic polymer thin films was slower with a sigmoidal shape at pH 1.2 and pH 8.0 with a maximum release of PCT after approximately 150 and 140 min, respectively. The release profile from thicker agarose films was between those of the thin films. Agarose blended with chitosan or synthetic polymers formed films with biphasic release behavior. Chitosan linearized the initial section of the release profile in chitosan/polymer blends. The automated procedure for release testing offers the advantage of low-cost, labor-effective and error-free data acquisition. The procedure has been validated as a useful microplate assay option for release profile testing.

Robotic microplate voltammetry for real-time hydrogel drug release testing.

Robotic square wave voltammetry (SVW) in 24-well microtiter plates has been developed as a reliable non-manual procedure for quantifying drug release from pharmaceutical hydrogels. The assay was established using 1% agarose disks containing Paracetamol® (PCT) as a model preparation. Computerized buffer delivery and SVW in calibration and hydrogel sample wells were performed by a three-electrode arrangement combined with a thin plastic tube. For the glassy carbon working electrode of the assembly the upper limit of the linear response and the lower detection limit of sequential 'in-well' PCT-SVW were 1000 and 0.5 µM, respectively. During non-stop runs through plate wells with equal drug titers the voltammetric PCT signal was stable for at least 6 h. For the construction of drug-release curves with triplicate data points PCT-SVW was performed sequentially on three identical hydrogel samples in neighboring plate wells, preceded and followed by sensor calibrations for response validation. The results showed bi-phasic PCT release profiles exhibiting an initial rapid loss of the drug near the surface of the gel, followed by slowly decelerating release of more deeply buried drug and the dissipation of the concentration gradient that drives diffusion. The proposed automation of voltammetric testing generates reliable hydrogel drug release profiles without the need for operator intervention, avoiding human errors from monotonous manual electroanalysis and releasing skilled staff for other work. This approach is therefore suggested as an economic option for hydrogel dissolution testing in academic or industrial R&D, particularly when the required multi-parameter optimization creates many samples.