Miscibility of Poly(lactide-co-glycolide) in Supercritical fluids

Abstract

In a polymer based drug delivery system, the polymer material surrounds the drug and delivers the substance to the desired target. Poly(lactide-co-glycolide) (PLGA) is the most widely used control-release system for many drugs with a short half-life, low stability, easy decomposition, and non-toxic side effects. Supercritical fluid (SCF) technology can be used to prepare or micronize drug-loaded particles without additional purification or cleaning procedures. In this work, the liquid–liquid phase transition of PLGA in several supercritical fluids, such as dimethyl ether (DME), CO2, chlorodifluoromethane (HCFC-22), and trifluoromethane (HFC-23), has been investigated. PLGA with a higher content of glycolide in the copolymer backbone shows upper critical solution temperature (UCST)-type phase behavior. Alternatively, in supercritical HCFC-22, lower critical solution temperature (LCST)-type phase behavior has been observed. The ratio of lactide to glycolide in the PLGA copolymer backbone majorly controls the phase behavior including the pressure–temperature (p-T), temperature-polymer weight fraction (T-w), pressure-density (p-ρ), and temperature-density (T-ρ) isopleths. The phase behaviors of PLGA in SCF CO2 and DME change from UCST- to LCST-type behavior with an increase in the lactide content. In contrast, PLGA in SCF HCFC-22 exhibits LCST-type phase behavior for all PLGA copolymers irrespective of the lactide content. Such phase behaviors are described well by the perturbed-chain statistical associating fluid theory (PC-SAFT) in a wide range of temperature (300–395 K) and pressure (3–310 MPa) with temperature-independent binary interaction parameters. In addition, significant differences have been observed in the solubility of PLGA in different SCFs; CO2 being the poorest solvent, and HCFC-22 being the best solvent.