Reverse engineering of Perseris and development of compositionally equivalent formulations

Area of Science:

• Pharmaceutical Sciences
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Injectable, long-acting in situ forming implants using poly(lactide-co-glycolide) (PLGA) and N-Methyl-2-Pyrrolidone (NMP) are established drug products.
• Lack of generic options for these complex formulations increases patient costs.
• Challenges in PLGA manufacturing and characterization hinder generic development.

Purpose of the Study:

• To comprehensively characterize the Perseris (risperidone) in situ forming implant.
• To develop compositionally equivalent risperidone implant formulations.
• To evaluate the in vitro performance of developed formulations.

Main Methods:

• Reverse engineering to identify critical quality attributes of Perseris PLGA and risperidone.
• Characterization of PLGA properties (MW, L/G ratio, end group, blockiness, Tg) and risperidone powder (crystal form, particle size).
• Development and evaluation of novel formulations using customized PLGA and a new adapter-based dissolution method.

Main Results:

• Key physicochemical properties of Perseris components were identified.
• Two compositionally equivalent formulations demonstrated comparable in vitro release and swelling profiles to Perseris.
• The novel dissolution method proved effective for controlled release assessment and formulation comparison.

Conclusions:

• Successful characterization of Perseris enables the development of compositionally equivalent formulations.
• Developed formulations exhibit similar in vitro performance, paving the way for potential generic products.
• The established methodology and novel dissolution technique are valuable for future long-acting implant development.