In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use
Spironolactone (SPL), a potent anti-aldosterone steroidal drug used to treat several diseases in paediatric patients (e.g., hypertension, primary aldosteronism, Bartter’s syndrome, and congestive heart failure), is not available in child-friendly dosage forms, and spironolactone liquids have been reported to be unpalatable. Aiming to enhance SPL solubility in aqueous solution and overcome palatability, herein, the effects of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) were thoroughly investigated on solubilisation in water and on masking the unpleasant taste of SPL in vivo. Although the complexation of SPL with HP-β-CyD was demonstrated through phase solubility studies, Job’s plot, NMR and computational docking studies, our in vivo tests did not show significant effects on taste aversion. Our findings, on the one hand, suggest that the formation of an inclusion complex of SPL with HP-β-CyD itself is not necessarily a good indicator for an acceptable degree of palatability, whereas, on the other hand, they constitute the basis for investigating other cyclodextrin-based formulations of the poorly water-soluble steroidal drug, including solid dosage forms, such as spray-dried powders and orodispersible tablets.
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About this article: Lopalco, A.; Manni, A.; Keeley, A.; Haider, S.; Li, W.; Lopedota, A.; Altomare, C.D.; Denora, N.; Tuleu, C. In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use. Pharmaceutics 2022, 14, 780. https://doi.org/10.3390/pharmaceutics14040780
Materials
For the UV/Vis spectroscopy method, Job’s plot and NMR studies, SPL was supplied by Farmalabor SRL (Canosa di Puglia, BT), and HP-β-CyD MW ~1460 was purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany).
For the HPLC studies, HP-β-CyD was kindly donated by FarmaLabor (Canosa di Puglia BT, Italy). Acetonitrile (ACN, HPLC grade) and purified water (Ph. Eur.) were purchased from Carlo Erba s.r.l. (Milan, Italy). For the human taste panel, SPL was supplied by Fagron, UK, and KLEPTOSE® HP-β-CyD Oral grade was supplied by Roquette, France.
The SPL and CyDs purchased from different suppliers had to be of pharmaceutical grade for human consumption in the sensory panel. Moreover, CyDs used in the experiments were characterised by the same degree of substitution