The role of glycyrrhizic acid in colloidal phenomena of supersaturation drug delivery systems containing the antifungal drug griseofulvin

• Published in: Journal of molecular liquids Vol. 301; p. 112336
• Main Authors: França, Maria Terezinha, Martins Marcos, Tatyane, A. Costa, Paulo F., P. Gerola, Adriana, Stulzer, Hellen Karine
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2020
• Subjects: Glycyrrhizic acid; Griseofulvin; phase separation; Poorly soluble drug; Precipitation inhibitor; supersaturation; PLM; Precipitation inhibitor; Poorly soluble drug; phase separation; Glycyrrhizic acid; FaSSIF; DLS; GA; GSF; Griseofulvin; supersaturation; PBpH6.5
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2019.112336

The ability of carriers to inhibit precipitation may determine supersaturating drug delivery systems capability of improving poorly soluble drugs bioavailability. It was hypothesized that glycyrrhizic acid (GA), a potential drug solubility enhancer, could act as a precipitation inhibitor in supersaturated solutions of the poorly soluble drug griseofulvin. Also, it was investigated the effect of biorelevant medium on GA colloidal formation and on drug phase separation. Phase separation studies were monitored by UV–Vis relative light scattering, UV absorbance, drug fluorescence intensity, dynamic light scattering and polarized light microscopy. The impact of biorelevant medium on GA colloidal properties was evaluated by conductivity, dynamic light scattering and pyrene fluorescence. GA maintained high drug supersaturated solution concentration in buffer pH6.5 (>0.38mmolL−1) and FaSSIF (>0.60mmolL−1) for 4h. The FaSSIF+GA combination provided a colloidal microenvironment polarity similar to organic solvents even in aqueous medium, increasing the maximum free drug concentration (0.89mmolL−1) before phase separation and impacting on precipitation type. Amorphous aggregates, obtained under these conditions, can sustain high free drug concentrations in gastrointestinal tract. The significance of this paper is to show the use of GA as an effective tool to overcome the biopharmaceutical limitations of a poorly soluble drug, such as GSF, enlightening the GA ability to form aggregates/micelles at biorelevant medium that could act as precipitation inhibitor. [Display omitted] •Glycyrrhizic acid acted as a precipitation inhibitor on supersaturated solutions.•Amorphous aggregates are formatted under griseofulvin supersaturation condition.•Glycrrhizic acid+biorelevant medium reduces solution microenviromental polarity.