gamma CD/HP gamma CD Mixtures as Solubilizer: Solid-State Characterization and Sample Dexamethasone Eye Drop Suspension

Purpose. Study the complexation of dexamethasone in combinations of gamma-cyclodextrin (gamma CD) and 2-hydroxypropyl-gamma-cyclodextrin (HP gamma CD) with emphasis on solid characterization and development of aqueous dexamethasone eye drop suspension for drug delivery through sclera. Methods. Dexamethasone/cyclodextrin (dexamethasone/CD) solid complex systems were prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and by in vitro drug dissolution testing. Sample eye drop suspensions were prepared applying solubilizer/suspender consisting of gamma CD/HP gamma CD mixtures, poloxamer 407 (P407) and polyvinylpyrrolidone. The eye drop suspension was characterized by its physicochemical properties. Results. The solid characterization techniques applied suggested that solid complexes were being formed. The results indicated that dexamethasone formed non-inclusion or micelle-like aggregates with HP gamma CD and the gamma CD/HP gamma CD mixture. The dissolution and dexamethasone release from the solid dexamethasone/gamma CD/HP gamma CD complexes was much faster than from the solid dexamethasone/gamma CD and dexamethasone/HP gamma CD complexes. The diameter of the solid particles in the dexamethasone eye drop suspension formulations were in all cases less than 10 mu m with a mean diameter from 2.5 to 5.8 mu m. The particle size decreased with increasing amount of P407. Permeation studies through semipermeable membrane and porcine sclera showed that increasing the amount HP gamma CD could enhance drug transport through the membrane barriers and this was related to enhanced drug solubility. The permeation rates were, however, decreased compared to formulation containing gamma CD alone due to larger hydrodynamic diameter of dexamethasone/gamma CD/HP gamma CD complex aggregates. All formulations were both chemically stable for at least 8 months at 25 degrees C and 40 degrees C. Conclusions. Combination of gamma CD and HP gamma CD, i. e., formation of dexamethasone/gamma CD/HP gamma CD complexes, resulted in synergistic effect. That is the mixture had greater solubilizing effect than the individual CD, resulted in enhanced dissolution and drug delivery through membranes. Furthermore, it is possible to control the drug release rate by adjusting the gamma CD:HP gamma CD ratio in the solid dexamethasone/gamma CD/HP gamma CD complexes.