Enhanced Dissolution Efficiency of Zaleplon Solid Dispersions via Modified β-Cyclodextrin Molecular Inclusion Complexes

Abstract

The focus of the current study is to confirm the potential of chemically modified cyclodextrins (methyl-β-cyclodextrin (MβCD/Kleptose® Crysmeb), hydroxypropyl-β-cyclodextrin (HP-β-CD/Kleptose® HPB) and sulfobutylether-β-cyclodextrin (SBE-β-CD/Captisol®)) to improve the dissolution rate of zaleplon in oral delivery. Native and modified cyclodextrins were screened via phase solubility studies in order to select the most efficient cyclodextrin in formation of stable inclusion complexes. A L-type phase solubilization resulted from phase solubility diagrams of all cyclodextrin indicated a linear proportional relation between the solubility of zaleplon versus different CD concentrations. Complexation with crysmeb and HP-β-CD resulted in greater complexation constant values and higher percentage complexation efficiency values. Therefore these two cyclodextrins were selected for formulation development. Inclusion complexes of zaleplon:cyclodextrin solid dispersions were prepared using lyophilization and spray-drying techniques. DSC and XRD performance delineates the transformation of crystalline form of zaleplon to amorphous state. 1HNMR studies confirm the presence of drug in the hydrophobic cavity of cyclodextrins and reveal the amorphous nature of the formulations. The stability studies of inclusion complexes for 60 days at 25 °C/60 % RH and 40°C/75%RH resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. In conclusion, in vitro dissolution studies displayed an overall two-fold improvement in the dissolution rate compared to pure drug attributed to Crysmeb and HP-β-CD as suitable complexing agents in enhancing the solubility of zaleplon.