Abstract
Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature.
Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of beta-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG.
Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G '') moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells.
Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p < 0.001) from 3.65 +/- 0.43 to 34.30 +/- 8.90 (dextran) and 805.80 +/- 5.30 (PEG) 24 h after polymer addition. In vitro release profiles showed significantly (p < 0.05) reduced AUC(0-8) (h), k and percentage of drug released from two-phase systems compared to beta-glucan dispersions, with the PEG system resulting in the lowest amount released over 8 h (15.1 +/- 1.6%).
Discussion: The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense beta-glucan gel.
Conclusion: 1.5% (w/w) beta-glucan combined with PEG at a ratio of 1: 3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release.