Continuous preparation of long-acting hydromorphone PLGA microspheres using an automatic and scalable microfluidic...

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Chemical Engineering

Background:

• Chronic pain management requires effective long-acting drug delivery systems.
• Poly-lactic-co-glycolic acid (PLGA) microspheres offer a promising platform for sustained drug release.
• Current manufacturing methods for microspheres can lack scalability and precise control.

Purpose of the Study:

• To develop and prepare long-acting hydromorphone-loaded PLGA (HM-PLGA) microspheres for chronic pain management.
• To utilize a novel automatic and scalable microfluidic process system for microsphere production.
• To investigate the impact of formulation parameters on microsphere properties using process analytical technology (PAT).

Main Methods:

• Development of an automated microfluidic system incorporating a micro-mixer, syringe/HPLC pumps, and process Raman spectroscopy.
• Systematic investigation of formulation parameters to control microsphere properties like particle size.
• Characterization of HM-PLGA microspheres using various analytical techniques.
• Pharmacokinetic studies in ICR mice and in vivo drug release studies in beagle dogs.

Main Results:

• Successfully prepared long-acting injectable homogeneous HM-PLGA microspheres with tunable particle size.
• Achieved a maximum drug-loading capacity of 7.71% and encapsulation efficiency of 69.40%.
• Pharmacokinetic studies demonstrated prolonged hydromorphone exposure in plasma compared to injection.
• In vivo studies confirmed sustained drug release from HM-PLGA microspheres for over 11 days.

Conclusions:

• The novel automatic microfluidic process system is effective for developing particle size-controllable, drug-loaded microspheres.
• This system shows potential for the continuous manufacturing of long-acting injectable formulations.
• HM-PLGA microspheres represent a viable strategy for effective chronic pain management through sustained hydromorphone delivery.