Formulations containing large doses of highly soluble active pharmaceutical ingredients (APIs) are especially challenging, in particular due to the risk that the drug is released too fast (burst release). The maximum tolerated concentration in the blood can then be exceeded, inducing toxicity and causing side effects. This risk can be ameliorated by applying multiple administrations, however at the expense of a lower patient compliance and incurring in higher healthcare costs.<br/>These issues can be solved by using polymeric matrices that ensure sustained release formulations with the intended pharmacokinetics.<br/>Despite the need for sustained release drug formulations, the number of commercialized drug products including a highly dosed and highly soluble API is limited. This is mainly attributed to the lack of suitable polymers that allow to sustain the release of these challenging compounds. Poly(2-oxazoline)s (PAOx) has demonstrated to be an excellent polymer platform to develop such formulations. In addition to their biocompatibility and stealth behavior, PAOx show a high synthetic versatility, allowing to finely tune the hydrophilic/hydrophobic balance of the polymer by varying the side chain composition.<br/>In the present work, the design and synthesis of PAOx of different hydrophilicity will be shown. Well-defined polymers with molecular weights above 50 kDa were synthesized. These polymers were used as matrix excipients for the formulation of a variety of APIs via different routes, including direct compression, hot melt extrusion (HME) and HME coupled with injection molding (HME/IM). PAOx show a high thermal stability, which is of importance for their processability.<br/>The release profile of the API could be tuned by variation of the polymer hydrophilic/hydrophobic balance. In our work we demonstrated that drug loads up to 70% API, 30% polymer (w/w) were possible using high molar mass PAOx. The possibility of controlling the dissolution kinetics of APIs using different PAOx blends was also investigated.

Poly(2-oxazoline)s as matrix excipient for sustained release formulations

2019 Spring National Meeting

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