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

Pharmaceutics
Anna KromeKarl Wagner

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 precli...Continue Reading

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Citations

Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nils BöhringerTill F Schäberle
Apr 15, 2021·International Journal of Pharmaceutics: X·Rafael D BachmaierKarl G Wagner

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Methods Mentioned

BETA
differential scanning calorimetry
reversed phase chromatography
Assay

Software Mentioned

STAR e
SimulationsPlus
PKPlus
Perkin
Elmer Spectrum
GastroPlus

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