Studies of cyclodextrin inclusion complexes. I. The salbutamol-cyclodextrin complex as studied by phase solubility and DSC

Abstract

Cyclodextrins (CYDs) are cyclic non-reducing oligosaccharides built up from six, seven or eight glucopyranose units (α-, β- or γ-CYD, respectively). Many drugs are able to form an inclusion complex with CYDs, being trapped entirely or at least partially into their slightly apolar cavities. Complexes of CYDs and salbutamol were obtained in both the liquid and solid state. The influence of both temperature and CYD concentration on complex solubility was studied using the method of Higuchi and Connors ( Adv. Anal. Chem., 4 (1965) 117–212). This is based on monitoring changes in the solubility of substrate (salbutamol) on the addition of complexing agents (α-, β-, Me-β- and γ-CYD). The rate of increase in substrate solubility with CYD concentration varied with the type of CYD used (Me-β->β-⪢γ->α-CYD). As salbutamol is water soluble and an A L type diagram is obtained, the solid complex was prepared by freeze-drying (lyophilization). In order to confirm solid complex formation, differential scanning calorimetry (DSC) was used. When guest molecules are incorporated in the CYD cavity, their melting, boiling or sublimation points usually shift to a different temperature or disappear within the temperature range where the CYD is decomposed. The thermograms obtained showed an endothermic peak for the freeze-dried salbutamol and for the physical mixture (salbutamol and β-CYD both freeze-dried) which was eliminated for the inclusion complex.