Science & Research

Advanced Analytical Techniques for Mixed Polymer Drug-Delivery Systems

Principal Investigator: Kinam Park

Performer: Akina Inc

Project Duration: 09/23/2016 – 09/23/2018

Regulatory Science Challenge:

Poly(lactide-co-glycolide) (PLGA) is a FDA-approved biodegradable polymer that can be made into microspheres for controlled-release drug delivery. Not only is the polymer robust and biocompatible, its mechanical properties, long clinical experience, and wide range of degradation times have led the polymer to be used as the vehicle in many different sustained drug release formulations. In particular,PLGA polymers have been developed as long-acting injectable (LAI) depot formulations.

While PLGA-based depot formulations made of a single type of PLGA can be easily characterized, reference formulations containing two different types of PLGA polymers can make identification challenging. Because the usual assays give only the “average” properties of a PLGA blend, there is a need to develop an assay protocol that can differentiate, distinguish, identify, and characterize the different types of PLGA polymers in each blend. The ability to compare different PLGA polymers quantitatively is important for the FDA, as understanding these key properties will enable the FDA to verify that the performance of multi-component PLGA depot formulations is maintained between generic products and their respective reference formulations. This will help ensure the safety and efficacy of PLGA-based generic drug products.

Project Description & Goals:

This project is to develop an assay for separating, distinguishing, and identifying two different types of PLGA polymers present in an individual LAI formulation. Researchers from Akina Inc proposed to first prepare a series of PLGA standards with known L:G ratios (ratio of lactide:glycolide in the polymer) and characterize their partial solubility parameters—dispersive, polar, hydrogen bonding, and total solubility—and Teas graph (also known as the solubility map). Since the solubility map of an individual PLGA is derived from their partial solubility parameters, which are based on the polymer’s interactions with various solvents, such a map serves as a unique profile characteristic to the polymer’s L:G ratio. Using these profiles, the L:G ratio of an unknown sample can be determined by matching and comparing its solubility map with those of PLGA standards.

Because the analytical protocol is designed to characterize commercial LAI formulations containing two different types of PLGA polymers, fractions obtained from two Treslstar® formulations—FDA-approved injectable depot formulations that are believed to consist two different PLGA polymers, specifically the formulations used for delivering 11.25mg and 22.5mg of drug for 3 and 6 months respectively—will be characterized fully for their weight average and number average molecular weights, polydispersity index, L:G ratio, endcap type, and the four aforementioned partial solubility parameters. Together, this 9-paramter characterization along with the solubility map will enable the FDA to identify the types of PLGA used in any PLGA blended formulations, and determining whether PLGAs used in generic products are qualitatively (Q1) and quantitatively (Q2) the same as the reference listed drug.

Achievements:

  • Assay of PLGA Types in Microparticle Depo Formulations (Internal poster, FDA Workshop: Demonstrating Equivalence of Generic Complex Drug Substances and Formulations, October 6, 2017)
  • The Effect of Lactide:Glycolide Ratio on PLGA Solubility in Selective Solvents (Internal poster, FDA Workshop: Demonstrating Equivalence of Generic Complex Drug Substances and Formulations, October 6, 2017)

Page Last Updated: 11/16/2017
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