Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties

Abstract

Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al³⁺. The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2² randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 μm and from 0.641 to 0.796 μm, respectively. The increase of polymer concentration (1–2%) and crosslinker concentration (3–5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.

Keywords:

• Colonic drug delivery
• dissolution test
• ionotropic gelation
• mucoadhesion
• multiparticulate system

Acknowledgements

This work is dedicated to the memory of our dearest Professor Raul Cesar Evangelista.

The authors are thankful to CNPq (Centro Nacional de Desenvolvimento Científico e Tecnológico), to FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), to CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and to Faculdade de Ciências Farmacêuticas de Araraquara – UNESP for providing financial and structural support to develop this work.

Declaration of interest

The authors report no declarations of interest.