Journal article
Development of stable liquid formulations for oligonucleotides.
- Poecheim J Roche Pharmaceutical Development & Supplies, PTD Biologics Europe, F. Hoffmann-La Roche Ltd, Basel, Switzerland; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Graeser KA Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
- Hoernschemeyer J Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
- Becker G Roche Analytical Research and Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Storch K Roche Pharmaceutical Development & Supplies, PTD Biologics Europe, F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: kirsten.storch@roche.com.
- Printz M Roche Pharmaceutical Development & Supplies, PTD Biologics Europe, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- 2018-05-27
Published in:
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. - 2018
Biopharmaceuticals characterization
Forced conditions
Formulation
Oligonucleotides
Stability
Acetylgalactosamine
Drug Carriers
Drug Compounding
Drug Stability
Excipients
Gamma Rays
Hydrogen-Ion Concentration
Oligonucleotides
Solutions
Sterilization
English
Oligonucleotide-based therapeutics have been implemented as a new therapeutic modality in biotech industry, which offers the opportunity to develop formulation platforms for robust parenteral formulations. The aim of this study was to gain a better understanding of stabilizing/de-stabilizing effects of different formulation parameters on unconjugated and N-acetylgalactosamine (GalNAc) conjugated single stranded oligonucleotides with locked nucleic acid modifications (LNA SSO), as model oligonucleotides. Various buffer systems, pH levels and different excipients were evaluated to optimize conditions for LNA SSO in liquid formulations. LNA SSO were exposed to different temperature conditions, mechanical stress as well as oxidative conditions, and the maximum feasible LNA SSO concentrations regarding handling and processing were determined. Finally, options for terminal sterilization of LNA SSO were evaluated. Results show that the tested LNA SSO were most stable under slightly alkaline conditions. A decrease in viscosity was best accomplished in the presence of spermine and lysine. Heat treatment and gamma irradiation caused high levels of degradation of the LNA SSO. Crucial formulation parameters, as identified in this study, should contribute to a significant increase in future productivity in drug product development for single-stranded oligonucleotides.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1016/j.ejpb.2018.05.029
- PMID 29802983
- Persistent URL
- https://sonar.ch/global/documents/232310
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