Biodegradable pseudolatexes: the chemical stability of poly(D,L-lactide) and poly(epsilon-caprolactone) nanoparticles in aqueous media.
Pseudolatexes of the biodegradable polyesters poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL) have been developed as potential aqueous coatings for sustained release. Since PLA and PCL are known to hydrolyze, the influence of the surfactant system, temperature, pH, and particle size on the chemical stability of the polymers as aqueous colloidal dispersions was investigated. Pseudolatexes of PLA and PCL formulated with a nonionic surfactant system were the most stable. When these dispersions were stored in unbuffered media for 350 days at 5 degrees C, only small changes in the weight-average molecular weights (Mw) of the polymers were observed. At 37 degrees C there was rapid degradation of both polymers in the dispersions. Arrhenius plots for the degradation of PLA and PCL resulted in a linear relationship for PCL. The nonlinear relationship for PLA was attributed to the polymer being in two different physical states within the 5 to 37 degrees C range which was used for the Arrhenius plots. PCL was in the rubbery state at all temperatures studied. Storage of the pseudolatexes in pH 1.65 buffer at 37 degrees C catalyzed the rates of degradation of both PLA and PCL. However, refrigeration of the pseudolatexes stabilized the polymers even at pH 1.65 for up to 4 months. Particle size had an insignificant effect on PLA and PCL stability in pseudolatexes prepared with either a nonionic or an anionic surfactant system.
Coffin
M D
MD
Glaxo Inc., Research Triangle Park, North Carolina 27709.
McGinity
J W
JW
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D013501:Surface-Active Agents; D013696:Temperature; D014867:Water
D011091:Polyesters; D013501:Surface-Active Agents; D014867:Water; C016240:polycaprolactone; C033616:poly(lactide)