In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use

被引:10
作者
Lopalco, Antonio [1 ]
Manni, Annachiara [2 ,3 ]
Keeley, Alexander [2 ]
Haider, Shozeb [2 ]
Li, Wenliang [4 ,5 ]
Lopedota, Angela [1 ]
Altomare, Cosimo Damiano [1 ]
Denora, Nunzio [1 ]
Tuleu, Catherine [2 ]
机构
[1] Univ Bari Aldo Moro, Dept Pharm Pharmaceut Sci, I-70125 Bari, Italy
[2] UCL, Sch Pharm, 29-39 Brunswick Sq, London WC1N 1AX, England
[3] Univ Parma, Food & Drug Dept, Parco Area Sci 27-A, I-43124 Parma, Italy
[4] Imperial Coll London, South Kensington Campus, London SW7 2AZ, England
[5] Cranfield Univ, Sch Water Environm & Energy, Cranfield Water Sci Inst, Cranfield MK43 0AL, Beds, England
基金
欧盟地平线“2020”;
关键词
spironolactone; hydroxypropyl-beta-cyclodextrin; palatability; cyclodextrin inclusion; phase solubility study; brief-access taste aversion; human taste panel; paediatric formulation; HYDROXYPROPYL-BETA-CYCLODEXTRIN; TASTE-MASKING; BITTER TASTE; ORAL BIOAVAILABILITY; CHEMICAL-STABILITY; BARTTER-SYNDROME; SOLUBILITY; SUSPENSION; MEDICINES; ACCEPTABILITY;
D O I
10.3390/pharmaceutics14040780
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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)-beta-cyclodextrin (HP-beta-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-beta-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-beta-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.
引用
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页数:16
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