Kinetics of phase separation: trapping of molecules in nonequilibrium phases

Abstract

When solutions of molecularly nonuniform polymers in single solvents are rapidly (1 K/s) cooled into the two-phase region, up to 20% of the polymer mass and 1.5% of the solvent molecules that would be found in the more dilute phase (sol) under equilibrium conditions are instead found in the more concentrated phase (gel). The higher molecular weight material of the equilibrium sol is preferentially incorporated into the nonequilibrium gel, with a capture probability increasing linearly with log M. Qualitatively the observations can be explained by the following consideration: For high cooling rates the polymer coils shrink so rapidly that the mobility of some chains no longer suffices for their withdrawal from the overlap region with others in order to become part of the sol phase. Quantitative calculations performed on the basis of this concept demonstrate that all experimentally observed features can be well reproduced if two (measurable, but presently unknown) parameters are adjusted.

Microencapsulation by coacervation of poly(lactide-co-glycolide) IV. Effect of the processing parameters on coacervation and encapsulation

“…the phase separation promoter, is added at an increasing rate: 0.65-18 ml/min, respectively. These figures strongly support the conclusion by Heinrich and Wolf [23] that polymer coacervation is a non-equilibrated process whatever the way the phase separation is induced: cooling of the polymer solution in the study by Heinrich and Wolf [ 23 ] and addition of an immiscible polymer in this study.…”

“…Indeed, the instantaneous concentration of the coating polymer in the supernatant and coacervate phases might be at variance, depending on time. Furthermore, the molecular weight distribution of the coating polymer in each phase should depend on the rate of polymer precipitation, as stated by Iso et al [22], and analyzed later by Heinrich and Wolf [23]. At sufficiently high precipitation rates, polymer coils shrink so quickly that chains are not properly distributed between the two phases and a non-equilibrium distribution may persist until the microsphere solidification occurs.…”

Drug Microencapsulation by PLA/PLGA Coacervation in the Light of Thermodynamics. 1. Overview and Theoretical Considerations

“…In particular, although thermodynamic aspects of coacervation have extensively been discussed in polymer sciences, 23,32,102 the practical implication for microsphere formation and drug microencapsulation has only been scarcely considered. 25,75,76 For the coacervation of PLA/PLGA, a nonequilibrium phase separation process was recently postulated. 15 It was assumed that sufficiently high precipitation rates would lead to a fast shrinking of polymer coils, so macromolecular chains could not reach an equilibrium between the two phases.…”

Coating of indomethacin-loaded embolic microspheres for a successful embolization therapy

“…Actually, the insolubilization of this poorly hydrophobic polymer (with high oligomers content meaning the presence of more numerous carboxyl and hydroxyl groups) of considerable viscosity (inherent viscosity of 0.45-0.6 Â 10 À4 m 3 kg À1 ) by the introduction of coacervation agent (silicone oil) was accelerated and supposed to be controlled by coacervate droplets growth mechanism rather than by association of two spontaneously occurring processes (i.e. nucleation and growth of droplets) (Heinrich and Wolf 1990). Hence, the zone of 'stability window', related to the formation of stabilized coacervate droplets, was assumed to be reduced with displacement of this zone towards the right side of the ternary diagram ( Figure 4); signalling a premature precipitation of PLGA co-polymer (Benoit 1996).…”