Development of novel cilostazol-loaded drug delivery systems to enhance the solubility and bioavailability by adopting various solubility-improving techniques

Abstract

The objective of this study was to fabricate and compare various solubility-ameliorating cilostazol-loaded drug delivery systems in order to identify the best formulation with enhanced solubility, dissolution and oral bioavailability of poorly water-soluble cilostazol. The finest suited hydrophilic carrier, surfactants and oil for formulating contrasting drug delivery systems were designated by scrutinizing the drug solubility in 1% (w/v) aqueous solution of different polymers, 10% (w/v) of surfactants and 1 ml of oils. Furthermore, the cilostazol-loaded surface-attached solid dispersion (SA) was prepared with cilostazol/PVP/ sodium lauryl sulphate (SLS) at the optimized ratio of 3.0/0.75/1.5 (w/w/w), cilostazol-loaded solvent-evaporated solid dispersion (SE) and cilostazol-loaded solvent wetted solid dispersion (SW) were fabricated with cilostazol/PVP/SLS at the best suitable weight ratio of 3.0/3.0/1.5, respectively. The liquid self-nanoemulsifying drug delivery system (liquid SNEDDS) was composed of oil (peceol), surfactant (Tween 20) and co-surfactant (Labrasol) with cilostazol. The solid SNEDDS was fabricated with the optimized liquid SNEDDS and inert carrier (calcium silicate). Spray-drying technique was employed to attain all of the solid state products. Moreover, the physicochemical characteristics of all the optimized preparations were assessed by the SEM, DSC, PXRD and particle size analyzer. Additionally, aqueous solubility, dissolution and pharmacokinetics in rats was also performed against the cilostazol. Amongst the trialled excipients PVP, SLS, peceol, tween 20 and Labrasol exhibited better solubility and hence chosen as the utmost pertinent carriers for fabricating various cilostazol-loaded drug delivery systems. All the preparations enormously enhanced the solubility, dissolution and oral bioavailability of cilostazol against the pure drug powder due to improved wetting, reduced particle size and conversion to the amorphous state. The oral bioavailability was improved in this order SE> SW> SA> SNEDDS> drug powder. In particular, SE displayed the most elevated bioavailability of the drug (~4.0 fold) amongst each solubilization technique. Accordingly, cilostazol-loaded solvent evaprated solid dispersion (SE) formulated with spray-drying technique possibly will be a conceivable drug delivery system for oral administration of poorly water-soluble cilostazol with exceptionally well enhanced solubility and bioavailability.