John Garner

Akinalytics Publication Details PLGA-Branching Analysis Development for PLGA-Glucose/Sandostatin

Blog Post created by John Garner on May 9, 2019

In addition to linear chains, polymers can be synthesized into a variety of branched configurations  including star, comb, and semi-branched polymers. For several types of polymers, there are a variety of methods to measure and analyze the branching. However, no such method has existed for PLGA until just now. As part of a collaboration effort with the Food and Drug Administration Office of Generic Drugs, Akina has developed methods around GPC-4D which enable characterization of branching in branched PLGAs including PLGA-Glucose used in Sandostatin. This and other evaluation techniques are available through the Akinalytics group (http://www.akinalytics.com/). Read more: Hadar, Justin, Sarah Skidmore, John Garner, Haesun Park, Kinam Park, Yan Wang, Bin Qin, and Xiaohui Jiang. “Characterization of branched poly (lactide-co-glycolide) polymers used in injectable, long-acting formulations.” Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919302421

 

“Abstract: Poly(lactide-co-glycolide) (PLGA) has been used in many injectable, long-acting depot formulations. Despite frequent use of PLGA, however, its characterization has been limited to measuring its molecular weight, lactide:glycolide (L:G) ratio, and end-group. These conventional methods are not adequate for characterization of unique PLGA polymers, such as branched PLGA. Glucose-initiated PLGA (Glu-PLGA) has been used in Sandostatin® LAR Depot (octreotide acetate for injectable suspension) approved by the U.S. Food and Drug Administration (FDA) in 1998. Glu-PLGA is a branched (also known as star-shaped) polymer and determining its properties has been challenging. It is necessary to develop methods that can determine and characterize the branching parameters of Glu-PLGA. Such characterization is important not only for the quality control of formulations, but also for developing generic parenteral formulations that are required to have the same excipients in the same amount (qualitative/quantitative (Q1/Q2) sameness) as their Reference Listed Drug (RLD). In this study, an analytical technique was developed and validated using a series of branched-PLGA standards, and it was used to determine the branching parameters of Glu-PLGA extracted from Sandostatin LAR, as well as Glu-PLGAs obtained from three different manufacturers. The analytical technique was based on gel-permeation-chromatography with quadruple detection systems (GPC-4D). GPC-4D enabled characterization of Glu-PLGA in its concentration, absolute molecular weight, hydrodynamic radius and intrinsic viscosity. The plot of the branch units per molecule as a function of molar mass provides a unique profile of each branched PLGA. The Mark-Houwink plots were also used to distinguish different Glu-PLGAs. These ensemble identification methods indicate that the branch units of Glu-PLGAs extracted from Sandostatin LAR range from 2 (i.e., linear) at the lower end of the molecular weight to <4 for the majority (94%) of Glu-PLGA. Keywords: Branched PLGA Star-shape PLGA Sandostatin Q1/Q2 sameness Long-acting depot”

 

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