Impact of the manufacturing technique on the dissolution-enhancement functionality of PEG4000 in Cilostazol tablets

Abstract

Cilostazol was selected as poorly-soluble model drug to investigate the impact of the manufacturing method on the excipient functionality of PEG4000 at various levels. Powder blends were prepared by direct compression (DC), wet granulation (WG) and hot-melt extrusion (HME). Characteristics of these blends and their compressed tablets were investigated by standard techniques. Solid-state characterization was carried out using differential scanning calorimetry (DSC). While DC trials were found with no significant differences, WG and HME showed contrasting enhancement and retardation effects regarding the dissolution profile of Cilostazol tablets depending on the level of PEG4000 incorporated. The optimal enhancement of dissolution was obtained at 10% w/w PEG4000 for tablets prepared by HME. DSC analysis indicated that no solid solutions were formed at such low levels of PEG-4000during processing by either manufacturing techniques. Consequently, the wetting functionality and dissolution enhancement of PEG4000 was revealed to be level- and manufacturing method dependent.