Modified starch as a new co-excipient in hydrophilic gels for prolonged drug delivery

Abstract

The hydrogels with methylene blue (MB), based on selected synthetic and semisynthetic polymers (SP), doped with citrate starch (CS), was evaluated successfully in the terms of MB release from polymeric matrix with prolonged release effect. The hydrophilic matrix in the hydrogel systems affects drug release, systemic absorption and therapeutic effect. The aim of the work was to investigate the use of citrate starch (CS) as an experimental drug carrier for cationic model drug—methylene blue (MB)—in the hydrogel formulation. The native potato starch was modified via esterification and crosslinking with 2.5 and 10.0% (w/w) of citric acid in 120 °C.

The hydrogels of methylcellulose (MC), polyacrylic acid (Carbopol^® 980 NF, C980) and crosspolymer 11 polyacrylate (Aristoflex^® Velvet, AV) were prepared and doped with native and citrate starches (NS and CS, respectively). The hydrogels without starches were applied as control samples. The release profiles were evaluated in zero-order, first-order, second-order kinetic models, as well as in Higuchi, Korsmeyer–Peppas and Weibull models. The analytical methods as: pH measurements, Fourier transform infrared spectroscopy (ATR-FTIR) as well as scanning electron microscope (SEM), were evaluated. The release kinetics of MB from the MC-based hydrogels matched the Korsmeyer–Peppas and the Higuchi models, while the MB release from C980- and AV-based hydrogels were suited to second-order and the Korsmeyer–Peppas kinetic models.

The lowest amount of MB was released after 240 min from AV-based hydrogels with CS addition. In the formulations of C980- and AV-based, both without and containing starch the prolonged MB release was observed, as compared to MC-based formulation. Moreover the citrate starch addition resulted in increased acidity of evaluated hydrogels. The FTIR analysis indicated interactions between the starches and the hydrophilic polymers, as well as between the starches and MB. Moreover, the interactions between MB and C980 and AV were revealed. The most remarkable influence of citrate starches on the MB release was attributed to the content of carboxyl groups in the starches.

The studies underlined the validity of the use of the citrate starches, as additives, in synthetic and semisynthetic hydrophilic gels. The possibility to regulate the rate of release of the active substance by appropriate selection of hydrophilic polymer, as well as citrate starch with a selected number of carboxyl groups, may improve a topical and mucosal application of cationic drugs.

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Materials

Reagents used for the study were: Methylene Blue (MB, Reko, Dzierżoniów, Poland), Methylcellulose (MC, Sigma-Aldrich, Steinheim, Germany), Carbopol® 980 (C980, Lubrizol, Wickliffe, USA), Aristoflex® Velvet (AV, Clariant Produkte, Frankfurt, Germany), native potato starch (NS, PPZ, Niechlów, Poland), citrate starches (University of Life Sciences in Wroclaw), potassium dihydrogen phosphate (Lach-Ner, Neratovice, Czech republic), disodium hydrogen phosphate (Pol-Aura, Poland, Olsztyn), deionized water of 0.1 µS/cm purity, 18% NaOH solution (Stanlab Sp. J., Lublin, Poland).

Kobryń, J., Witkowska, A., Raszewski, B. et al. Modified starch as a new co-excipient in hydrophilic gels for prolonged drug delivery. Sci Rep 15, 19255 (2025). https://doi.org/10.1038/s41598-025-88179-x