Thumbnail Image
Publication

Solubility and Stability Enhanced Oral Formulations for the Anti-Infective Corallopyronin A.

Krome, Anna K
; 
Becker, Tim
; 
Kehraus, Stefan
; 
Schiefer, Andrea
; 
Steinebach, Christian
; 
Aden, Tilman
; 
Frohberger, Stefan J
; 
López Mármol, Álvaro
; 
Kapote, Dnyaneshwar
; ... show 9 more
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2020-11-18
Submitted date
Show all metadata
Files
Thumbnail Image
Open Access publication
Adobe PDF, 2.93 MB
Other Titles
Abstract
Novel-antibiotics are urgently needed to combat an increase in morbidity and mortality due to resistant bacteria. The preclinical candidate corallopyronin A (CorA) is a potent antibiotic against Gram-positive and some Gram-negative pathogens for which a solid oral formulation was needed for further preclinical testing of the active pharmaceutical ingredient (API). The neat API CorA is poorly water-soluble and instable at room temperature, both crucial characteristics to be addressed and overcome for use as an oral antibiotic. Therefore, amorphous solid dispersion (ASD) was chosen as formulation principle. The formulations were prepared by spray-drying, comprising the water-soluble polymers povidone and copovidone. Stability (high-performance liquid chromatography, Fourier-transform-infrared spectroscopy, differential scanning calorimetry), dissolution (biphasic dissolution), and solubility (biphasic dissolution, Pion's T3 apparatus) properties were analyzed. Pharmacokinetic evaluations after intravenous and oral administration were conducted in BALB/c mice. The results demonstrated that the ASD formulation principle is a suitable stability- and solubility-enhancing oral formulation strategy for the API CorA to be used in preclinical and clinical trials and as a potential market product.
Citation
Pharmaceutics. 2020 Nov 18;12(11):1105. doi: 10.3390/pharmaceutics12111105.
Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Publisher
MDPI
Journal
Pharmaceutics
URI
http://hdl.handle.net/10033/622647
DOI
10.3390/pharmaceutics12111105
PubMed ID
33217948
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1999-4923
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International
cb
Collections
publications of the research group of microbial drugs (MWIS)
publications of the scientific administration (GFW)