[Colloid-physical characterization of supramolecular drug delivery systems].
Cyclodextrins are well-known biocompatible oligosaccharides capable of forming inclusion complexes with suitable guest molecules. They can be expediently used as solubilizers for hydrophobic pharmacon molecules in aqueous solutions. In this study, the effect of colloidal and non-colloidal additives on the solubility of statins is described. Two statin-derivatives (lovastatin and simvastatin), beta-cyclodextrin (-CD) and randomly methylated beta-cyclodextrin (RAMEB) were used as complexing agents. Those pharmacons are widely used in the management of cardiovascular diseases involving high or elevated blood cholesterol levels. Complexation of the highly lipophilic statin molecules with beta-CD and RAMEB was studied in the presence and the absence of dissolved polyvinyl-pyrrolidone (PVP). For the characterization of the stability of statin-CD complexes, association constant of binary associates have been calculated. It was found that inclusion complexation can beneficially enhance the solubility of both statin-derivatives. In binary statin-CD solutions predominantly associates of 1:1 molar ratio form, which show significant surface activity. In polymer-containing ternary systems, the solubility of the pharmacons can further be increased. This phenomenon can presumably be explained with the formation of statin-CD-polymer ternary associates of supramolecular structure. In such supramolecular assemblies the amphiphilic statin-CD complexes are likely bound to the macromolecules' chains. The wetting properties of solid, dried and powdered complexes were studied by immersion enthalpy measurements. Both in binary and ternary systems a significant increase in the immersion enthalpy values could be detected, which indicates that the complexes exhibit fairly hydrophilic character.
Süle
András
A
ELTE TTK Kémiai Intézet Kolloid es Szupramolekuláris Rendszerek Laboratóriuma, Budapest, Pázmány Péter séány 1/A - H-1117. sule.andras@t-online.hu
Csempesz
Ferenc
F
D003102:Colloids / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D011208:Powders; D012995:Solubility
D003102:Colloids; D003505:Cyclodextrins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011208:Powders