Schoenhammer, K. and Petersen, H. and Guethlein, F. and Goepferich, A. (2009) Injectable in situ forming depot systems: PEG-DAE as novel solvent for improved PLGA storage stability. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 371 (1-2). pp. 33-39. ISSN 0378-5173, 1873-3476
Full text not available from this repository. (Request a copy)Abstract
Injectable in situ forming depots (ISFD) that contain a peptide or a protein within a polymeric solution comprise an attractive, but challenging application system. Beyond chemical compatibility, local tolerability and acute toxicity, an important factor for an ISFD is its storage stability as a liquid. In this study, poly(D,L-lactide-co-glycolide) (PLGA) degradation in the presence of poly(ethyleneglycol) (PEG) as bio-compatible solvent was investigated as a function of storage temperature and water content. The PLGA molecular weight (M-w) was determined by gel permeation chromatography (GPC) and monitored by NMR during degradation. Rapid PLGA degradation of 75% at 25 degrees C storage temperature was shown to be the result of a trans-esterification using conventional PEG as solvent. A significant improvement with only 3% M-w loss was obtained by capping the PEG hydroxy- with an alkyl- endgroup to have poly(ethyleneglycol) dialkylether (PEG-DAE). The formation of PEG-PLGA block co-polymers was confirmed by NMR, only for PEG300. Reaction rate constants were used to compare PLGA degradation dissolved in conventional and alkylated PEGs. The degradation kinetics in PEG-DAE were almost completely insensitive to 1% additional water in the solution. The transesterification of the hydroxy endgroups of PEG with PLGA was the major degradation mechanism. even under hydrous conditions. The use of PEG-DAE for injectable polymeric solutions, showed PLGA stability under the chosen conditions for at least 2 months. Based on the results obtained here, PEG-DAE appears to be a promising excipient for PLGA-based, parenteral ISFD. (C) 2008 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DRUG-DELIVERY SYSTEMS; PHASE INVERSION DYNAMICS; HYDROLYTIC DEGRADATION; PART II; MICROSPHERES; BIOMATERIALS; LEUPROLIDE; ACYLATION; IMPLANT; ACID); Poly(D,L-lactide-co-glycolide); Degradation; Stability; In situ forming depot |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Sep 2020 12:32 |
| Last Modified: | 17 Sep 2020 12:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29117 |
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