Injectable in situ forming depot systems: PEG-DAE as novel solvent for improved PLGA storage stability

International Journal of Pharmaceutics
Karin SchoenhammerAchim Goepferich

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 biocompatible solvent was investigated as a function of storage temperature and water content. The PLGA molecular weight (Mw) 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 transesterification using conventional PEG as solvent. A significant improvement with only 3% Mw 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 ...Continue Reading

References

Oct 21, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·K J BrodbeckA J McHugh
Apr 12, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Hatefi, B Amsden
Dec 14, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Christian MatschkeAlfred Fahr
Jan 29, 2003·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Andrea Lucke, Achim Göpferich
Oct 16, 2003·International Journal of Pharmaceutics·Gesine SchlieckerThomas Kissel
Aug 7, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·C B PackhaeuserT Kissel
Apr 14, 2006·Current Drug Delivery·Yasmin SultanaAsgar Ali
Sep 5, 2006·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Steven J SiegelNily Dan
Sep 12, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·W Y DongR Bodmeier
Sep 15, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·C B Packhaeuser, T Kissel
May 27, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·H Kranz, R Bodmeier

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Citations

Oct 2, 2009·Pharmaceutical Research·Karin SchoenhammerAchim Goepferich
Jan 1, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Raghu Raj Singh ThakurDavid S Jones
Feb 8, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Andreas SchädlichKarsten Mäder
Sep 25, 2014·Expert Opinion on Drug Delivery·Ravi VaishyaAshim K Mitra
Dec 29, 2015·International Journal of Biological Macromolecules·Zhixia GengZugong Yu
Jul 29, 2010·Journal of Pharmaceutical Sciences·Karin SchoenhammerAchim Goepferich
Jan 15, 2013·International Journal of Pharmaceutics·C Regnier-DelplaceJ Siepmann
May 1, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sabine Kempe, Karsten Mäder
Sep 5, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Marianne ParentAriane Boudier
Jun 7, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·M P DoF Siepmann
Oct 12, 2014·International Journal of Pharmaceutics·Amelia M Avachat, Sayali S Kapure
Nov 9, 2010·International Journal of Pharmaceutics·F KreyeJ Siepmann
Sep 1, 2010·Therapeutic Delivery·Andrew L Lewis, Lisbeth Illum
May 28, 2020·Pharmaceutics·Sonalika BhattaccharjeeAjay K Banga

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