Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Amphiphilic Copolymers for Long-Acting Injectables: Synthesis, Non-Acylating Performance and In Vivo Degradation

Abstract

This article presents the evaluation of diblock and triblock poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) amphiphilic copolymers (PEG-PTMCs) as excipients for the formulation of long-acting injectables (LAIs). Copolymers were successfully synthesised through bulk ring-opening polymerisation. The concomitant formation of PTMC homopolymer could not be avoided irrespective of the catalyst amount, but the by-product could easily be removed by gel chromatography. Pure PEG-PTMCs undergo faster erosion in vivo than their corresponding homopolymer. Furthermore, these copolymers show outstanding stability compared to their polyester analogues when formulated with amine-containing reactive drugs, which makes them particularly suitable as LAIs for the sustained release of drugs susceptible to acylation.

Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables

“…DB mPEG–PTMC and TB PTMC–PEG–PTMC copolymers, whose chemical structure is depicted in Figure 1 , were synthesized at MedinCell. Details around the synthesis and characterization of such polymers can be found elsewhere [ 25 ]. Pharma grade acetonitrile was acquired from Carlo Erba (Peypin, France) and USP grade dimethyl sulfoxide (DMSO) was purchased from Gaylord Chemical (Los Angeles, CA, USA).…”