Poly(ethylene carbonate) as a surface-eroding biomaterial for in situ forming parenteral drug delivery systems: a feasibility study.
To evaluate the technical feasibility of poly(ethylene carbonate), PEC, for injectable in situ forming drug delivery systems, the physical properties of PEC solutions were characterized. The solubility of PEC was investigated in different solvents, and the Hildebrand solubility parameters and Flory-Huggins interaction parameters of PEC were determined. By turbidity titration, the experimental ternary phase diagram of water-NMP/DMSO-PEC was constructed. NMP solution required more water to precipitate PEC compared to DMSO solution. The dynamic viscosity of PEC solution increased at lower temperature, higher polymer concentration and longer aging time. Differential scanning calorimetric (DSC) measurements confirmed only weak physical interactions in the system after aging, and the physical aging effect was thermo-reversible. Release of NMP from PEC formulations was twofold slower than that of DMSO at similar concentrations. The morphology of PEC depots after injection into aqueous solution was studied using scanning electron microscopy (SEM). A DMSO formulation of bovine serum albumin displayed less burst release than a NMP formulation. In summary, our investigations demonstrate that in situ depot forming systems can be obtained from PEC solutions. Moreover, a solution of PEC in DMSO would be preferred over NMP due to the reduced burst release.
Liu
Yu
Y
Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Marburg, Germany.
Kemmer
Annette
A
Keim
Klaus
K
Curdy
Catherine
C
Petersen
Holger
H
Kissel
Thomas
T
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D003692:Delayed-Action Preparations; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D016503:Drug Delivery Systems; D004356:Drug Storage; D005240:Feasibility Studies; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011095:Polyethylenes / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014783:Viscosity
D003692:Delayed-Action Preparations; D011095:Polyethylenes; D011760:Pyrrolidinones; D012997:Solvents; C039212:polyethylene carbonate; D012710:Serum Albumin, Bovine; C038678:N-methylpyrrolidone; D004121:Dimethyl Sulfoxide