Phase inversion dynamics of PLGA solutions related to drug delivery. Part II. The role of solution thermodynamics and bath-side mass transfer.
The role of solvent properties and bath-side composition on the phase inversion dynamics and in vitro protein release kinetics of polylactic-co-glycolic acid (PLGA) solutions has been examined using dark ground imaging, in vitro release rate, and SEM techniques. Thermodynamic phase diagrams for three model systems (PLGA in 1-methyl-2-pyrrolidinone (NMP), triacetin, and ethyl benzoate) suggest two general classes of precipitation behavior, depending on the relative solvent strength and water miscibility. Drug release from the NMP-based system is primarily governed by the dynamics of phase inversion and exhibits a distinct burst region followed by a much slower release. Alternatively, depots with low solvent/water affinity (PLGA in triacetin or ethyl benzoate) undergo much slower phase inversion, resulting in a less porous, more fluid, two-phase structure that also releases protein more uniformly. Addition of a small chain triglyceride or organic salt to the aqueous receptor bath also evokes a significant increase in the mass transfer rate of protein from the low solvent/non-solvent affinity depots. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given.
Brodbeck
K J
KJ
Department of Chemical Engineering, University of Illinois, Urbana 61801, USA.
DesNoyer
J R
JR
McHugh
A J
AJ
D000042:Absorption; D001565:Benzoates / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D011232:Chemical Precipitation; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000493:pharmacokinetics*; D011760:Pyrrolidinones / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D013997:Time Factors; D014215:Triacetin / Q000737:chemistry
D001565:Benzoates; D001672:Biocompatible Materials; D005782:Gels; D011108:Polymers; D011506:Proteins; D011760:Pyrrolidinones; D012996:Solutions; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C038678:N-methylpyrrolidone; D014215:Triacetin