Behaviour of Lipid-based Formulations Containing Nifedipine in Aqueous Media as Observed by Small Angle X-ray Scattering

摘要

Lipid-based formulations (LBF) including self-emulsifying drug delivery system have been used to improve drug dissolution and bioavailability by avoiding rate-limiting step during dissolution of poorly water-soluble drugs. This study was aimed to investigate the behavior of lipidbased formulations upon dilution in aqueous media by using small angle X-ray scattering (SAXS). LBF is composed of oil (caprylic/capric glyceride), surfactants (polyoxyl 35 castor oil or polyoxyl 40 hydrogenated castor oil), and co-solvent (diethylene glycol monoethyl ether) at a weight ratio of 1:1:8. Nifedipine, a poorly water-soluble drug, was used as a model drug. A 100-fold dilution of the LBF in aqueous media (i.e., simulated gastric fluid USP without pepsin (SGF) and distilled water) resulted in nano-sized emulsion (less than 200 nm). The selected formulations were diluted in aqueous media at various ratios (e.g., 0.01, 0.02, 0.04, 0.06, 0.09, 0.11, 0.18, 0.25, 0.67, 1.5, 4, 99, 199 and 300 folds) and then, after equilibrium, monitored by SAXS in order to observe the surfactant rearrangement. The results from SAXS scattering curves (q of 0.027-0.980 A~(-1)) demonstrated that a lamellar phase or liquid crystalline was not formed upon dilution. The emulsions were formed without the ordered structure.