(724i) Development of Drug-Polymer Composite Microparticles in a Microencapsulation Process Using Supercritical CO2

The supercritical antisolvent process has been widely utilized to fabricate drug-loaded polymer microparticles. Generally, the drug and polymer are both dissolved to obtain a homogeneous organic solution and sprayed into supercritical CO₂, the drug and polymer are co-precipitated to form drug-polymer composite microparticles. However, the co-precipitation process generates drug-loaded polymer microspheres accom­panied by relatively low drug load, low encapsulation efficiency, and no sustained release of the drug, since most of the drug is precipitated onto or just loosely attached to the surface of the polymer microparticles.

To improve the drug load, encapsulation efficiency, and sustained-release properties of supercritical CO₂-based drug-loaded polymer carriers, we have designed a novel process of suspension-enhanced dispersion by supercritical CO₂ (SpEDS), where an “injector” was utilized in the suspension delivery system. By suspending the methotrexate (MTX) nanoparticles in the poly (L-lactide)-poly(ethylene glycol)-poly(L-lactide) (PLLA-PEG-PLLA) dichloromethane solution and spraying the suspension into the supercritical CO₂, the MTX nanoparticles were microencapsulated via the precipitation of PLLA-PEG-PLLA on the surface of the particles. The resulting composite MTX-PLLA-PEG-PLLA microparticles had a mean particle size of 545 nm, drug loading of 13.7%, and an encapsulation efficiency of 39.2%. After an initial burst release, with around 65% of the total methotrexate being released in the first 3 hours, the MTX-PLLA-PEG-PLLA microspheres released methotrexate in a sustained manner, with 85% of the total methotrexate dose released within 23 hours and nearly 100% within 144 hours.

Similar experiments were also carried out to microencapsulate the puerarin nanoparticles by PLLA, the results also indicate that the SpEDS process successfully produced the drug-polymer composite microparticles with a higher drug load, encapsulation efficiency and longer sustained-release effect. Compared with a parallel study of the coprecipitation process, microencapsulation process using SpEDS offered greater potential to manufacture drug-loaded polymer microspheres for a drug delivery system.