Coloring of PLGA implants to better understand the underlying drug release mechanisms

Abstract

Different dyes and a colored vitamin (riboflavin) were used to better understand the underlying drug release mechanisms in poly(lactic-co-glycolic acid) (PLGA)-based implants. The latter were prepared by hot melt extrusion (HME) or formed in-situ, upon solvent exchange when injecting a PLGA solution in N-methyl-pyrrolidone (NMP) into phosphate buffer pH 7.4. Methylene blue was used as water-soluble dye to stain the release medium, riboflavin as a yellow, water-soluble "model drug", and Sudan-III-red as poorly water-soluble dye, incorporated in the implant. In the case of pre-formed HME implants, the "orchestrating" role of polymer swelling for the control of drug release could be visualized: At early time points, only limited amounts of water penetrate into the system, insufficient for noteworthy drug dissolution and diffusion. However, bulk erosion starts, and once a critical polymer molecular weight threshold value is reached, substantial implant swelling sets on: Large amounts of water come in and allow for significant drug dissolution and diffusion. In the case of in-situ forming implants, the importance of the composition of the liquid formulation for the resulting inner implant structure could be visualized. The latter affects the rate and extent at which water penetrates into the system and, thus, the resulting drug release rate.

Keywords: Diffusion; Drug release mechanism; Implant; PLGA; Swelling.