Method matters: Development of characterization techniques for branched and glucose-poly(lactide-co-glycolide) polymers

Defining the qualitative sameness of parenteral formulations comprised of poly(lactide-co-glycolide) (PLGA) requires assays of the relevant properties of polymer from each formulation. Gel-permeation chromatography with quaternary detection (GPC-4D) has been previously applied to other polymers, and the relevant mathematical parameters for their characterization are available; however, such parameters have not been described for branched PLGA polymers. Little information is available for the determination of glucose within glucose-PLGA (Glu-PLGA) branched polymers. This study describes the experimental methods of defining the mathematical parameters for characterization of branched PLGA polymers and the validation of these parameters using known branched-PLGA standards. The glucose, used as an initiator, was tracked through the synthesis of Glu-PLGA by both 13C NMR and enzymatic analysis. The analytical determination of the relevant parameters defining Glu-PLGA, such as the branching number, and the presence of glucose, requires the use of appropriate procedures experimentally validated in a systematic manner. The procedures described in this study were developed for characterization of Glu-PLGA with the lactide:glycolide (L:G) ratio of 55:45 used in Sandostatin® LAR. The procedures can also be used for characterization of Glu-PLGAs made of different L:G ratios. [Display omitted]