Effect of cyclodextrins on physico-chemical and release properties of Eudragit RS 100 microparticles containing glutathione

Abstract

The objective of this work was to develop a novel microparticulate system based on the mucoadhesive polymer Eudragit-RS 100 and cyclodextrins (CDs), potentially useful for the oral administration of Glutathione (γ–glutamylcysteinylglycine, GSH). For this purpose, an oil-in-oil (O/O) emulsion-solvent evaporation method was used for the preparation of microparticles (MPs) containing GSH alone or together with one of the following CDs: α-, β-, γ-, methyl-β-(Me-β-), hydroxypropyl-β-(HP-β-) or sulfobutylether-β-cyclodextrin (SBE_7m-β-CD). MPs were obtained by emulsifying a mixture of Eudragit RS 100, GSH, CD and magnesium stearate in acetone or acetonitrile with a mixture of liquid paraffin and Span 80. Size, encapsulation efficiency, and drug release of the prepared MPs were evaluated. The results clearly indicated that all the examined properties were dependent on the water-miscible solvents and CD used. In particular, MPs prepared by using acetone or acetonitrile showed different size distributions with mean diameters in the ranges 82–350 and 15–22 μm, respectively. Moreover, encapsulation efficiency values were found to be high in all cases (71–99%) and was significantly affected by the CD type. The GSH release rates were evaluated employing dissolution media with different pH values (1.2, 6.8 and 7.4) and the following rank order was obtained for MPs prepared using acetone: MPs incorporating Me-β-CD > MPs without CD > MPs incorporating the remaining CDs. On the other hand, MPs prepared using acetonitrile gave the highest GSH release rate. Finally, stability of GSH encapsulated in MPs containing HP-β-CD to enzymatic attack by pepsin A, α-chymotrypsin, and γ-glutamyltranspeptidase was also investigated.