Polyene formulations with increased water solubility

POLYENE FORMULATIONS WITH INCREASED WATER SOLUBILITY 

The soluble complexes of heptaenes commercially available are formulated with detergent-like substances, e.g. sodium desoxycholate or sodium lauryl sulphate, and do not form true solutions but consist of colloidal dispersions in an aqueous medium. The in vitro solubility of drugs with low aqueous solubility may be enhanced by coprecipitation with poly(vinyl pyrrolidone) (PVP) [376, 377]. The preparation of nystatin—PVP complexes has been described [378-380]. The solubility of PVP coprecipitates was eight to ten times greater than the parent compound [381] but the coprecipitates showed decreased antibiotic stability. 

Various polyene—ion complexes have been developed. Water-soluble complexes of amphotericin B with calcium and oxalic or succinic acids have been described [382]. Stable water-soluble borate complexes of amphotericin B, candidin, candicidin, pimaricin have been developed [383]. An advantage of producing stable water-soluble iron(Fe(II) and Fe(III))—polyene complexes was that complexes retained the in vitro antifungal properties of the parent compound [384] while water-soluble calcium complexes showed enhanced antifungal action [385] and it has been suggested that amphotericin B—meglumine complexes were less toxic when used intravenously than desoxycholate complexes [386]. 

The constrained nature of the macrocyclic lactone ring, the extensive unsaturation of the chromophore, and the variety of functional groups in the polyene molecule confers sensitivity to physical and chemical attack. Unfortunately, the resulting products are usually biologically inactive. Saturation of the chromophore or breaking the lactone ring by saponiflcation reduced the affinity for sterol, the antifungal properties and the haemolytic activity [197]. 

The first attempts to reduce the toxicity of polyenes and increase water 

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POLYENE FORMULATIONS WITH INCREASED WATER SOLUBILITY... 

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