A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson's disease

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Neuroscience

Background:

• Apomorphine, a dopamine agonist, effectively manages Parkinson's disease off episodes.
• Current apomorphine therapy requires three daily injections due to its short half-life.
• Frequent dosing presents significant compliance challenges for Parkinson's patients.

Purpose of the Study:

• To develop a novel deep eutectic-based formulation for sustained-release apomorphine.
• To reduce the dosing frequency of apomorphine therapy.
• To improve patient compliance in advanced Parkinson's disease treatment.

Main Methods:

• Formulation of a deep eutectic solvent (choline-geranate) with cosolvent (NMP) and stabilizer (PEG).
• Characterization of the formulation's self-emulsification into a microemulsion upon subcutaneous injection.
• Ex vivo studies using gels and rat skin to confirm sustained release mechanism.
• In vivo pharmacokinetic studies in rats and pigs, comparing with a clinical comparator.

Main Results:

• The deep eutectic formulation demonstrated spontaneous microemulsion formation upon injection, entrapping apomorphine.
• Ex vivo and in vivo studies confirmed significantly slowed apomorphine release and extended pharmacokinetics.
• Pharmacokinetic data in rats and pigs showed improved drug release profiles compared to the clinical comparator.
• Pharmacokinetic simulations suggested potential for thrice-weekly dosing in humans.

Conclusions:

• A novel deep eutectic formulation enables sustained release of apomorphine.
• This formulation has the potential to reduce apomorphine dosing frequency from daily to thrice-weekly.
• The developed formulation offers a promising strategy to enhance therapeutic compliance for Parkinson's disease patients.