Design of superdisintegrant- and effervescent agent-less dispersible fast-release melt pellets

Fast-release matrix utilizing superdisintegrants and effervescent agents was met with slow matrix disaggregation during dissolution and effervescence loss during storage, thereby delaying drug dissolution. This study employed electrolyte as alternative dispersant of fast-release matrix prepared using solvent-free melt pelletization technique which prevented instantaneous reaction between electrolyte and solvent during agglomeration and allowed such reaction to occur only in dissolution phase. The melt pellets were prepared using lactose and polyethylene glycol (PEG) 3000 as hydrophilic filler/binder, calcium acetate and calcium carbonate as electrolytes, tolbutamide as poorly water-soluble drug in free form and embedded in PEG 3000. These pellets were subjected to drug dissolution and physicochemical tests at molecular scale. The dissolution of tolbutamide in simulated gastric milieu increased following its formulation into pellets due to enhanced drug segregation and amorphization. A further increase in drug dissolution was attainable through pellet formulation with water-soluble calcium acetate instead of effervescent acid-soluble carbonate salt. Calcium acetate dissolved rapidly in aqueous medium to initiate turbulence in core matrix and fast pellet break-up through erosion and disintegration, unlike channeling agent. Small dispersible particles with elevated dissolution surface area were formed and had pellet fast-release characteristics unaffected by prolonged matrix storage.

Superdisintegrant- and effervescent agent-less fast-release pellets were designed with polar dispersible electrolyte as drug release inducer. Pellets formulated with electrolyte by melt agglomeration to avoid pre-reaction. Electrolyte solvation with liquid turbulence induced only during dissolution. In situ calcium acetate solvation vigour fragmentizes pellets and promotes drug release, unlike calcium carbonate which exhibits slow effervescence and has matrix drug release retarded.Figure optionsDownload as PowerPoint slideHighlights
► Superdisintegrant- and effervescent agent-less fast-release pellets
► Polar dispersible electrolyte as effective drug release inducer
► Pellets processed with electrolyte by melt agglomeration to avoid pre-reaction
► Electrolyte solvation with liquid turbulence induced only during dissolution
► In situ electrolyte solvation fragmentizes pellets and promotes drug release.