Sustained release drug products offer many advantages in comparison to conventional immediate release formulations by maintaining the desired drug plasma concentration within the therapeutic range over a longer time period. This results in improved effectiveness, less side-effects, greater compliance and lower costs. The development of sustained release matrix formulations is especially challenging for highly dosed and highly soluble active pharmaceutical ingredients (APIs) as the drug release is often too fast and/or shows a burst release. Several polymers are currently used for formulation of sustained release tablets. However, no commercially available polymers can ensure sustained drug release of highly soluble APIs with a drug load higher than 40% (w/w). In contrast to the currently available matrix formers, poly(2-oxazoline)s can sustain the release of slightly to freely soluble APIs with a drug load up to 70% (w/w). This is illustrated in the shown figure, comparing the dissolution profile of formulations consisting of metoprolol tartrate (MPT), a freely soluble API, and suitable commercial polymers with that of poly(2-sec-butyl-2-oxazoline) (PsecBuOx), a newly developed amphiphilic polymer for formulation. All formulations were processed on the same injection molding equipment. Compared to the formulation based on PsecBuOx, the drug release rate from the other formulations was similar or faster. However, it should be noted that the poly(2-oxazoline) based formulation included more than twice the drug load (i.e. 70% w/w MPT vs. 30% w/w MPT). These examples highlight the unique release sustaining capacity of poly(2-oxazoline)s for highly dosed, highly soluble APIs in comparison to polymers that are among the best currently available release sustaining polymers. In the present contribution, the synthesis of several high molar mass (&gt; 50 kDa) amphiphilic poly(2-oxazoline)s will be shown, followed by the dissolution kinetics of different APIs in formulations prepared via different routes, from direct compression to hot melt extrusion and injection molding. The ability to stir the dissolution profile by modulating the polymer hydrophilicity will also be displayed.

High-capacity matrix excipients for controlled drug release: surpassing the state-of-the-art

2019 Spring National Meeting

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