Formulation and hemolysis study of nonionic oil-in-water microemulsion

Abstract

The use of microemusion as drug delivery systems offers many advantages including increased drug solubility and absorption. The formulation of nonionic oil-in-water (o/w) microemulsion using pharmaceutical ingredients was studied. The physicochemical properties including particle size, size distribution and viscosity were investigated. In addition, the effect of the systems on erythrocyte hemolysis was determined. The nonionic microemulsions were formed using isopropyl myristate as oil, distilled water or buffer solution as aqueous phase and nonionic surfactant with or without cosurfatant. The surfactants used were Tween 20, Tween 80, Solutol HS15 and Cremophor EL and the cosurfactants were glycerol, propylene glycol, Palsgaard 0093 and Imwitor 308. Surfactant was mixed with cosurfactant at 4:1, 2:1 and 1:1 weight ratios of surfactant to cosurfactant. The phase behaviors of systems were compared. The formulations, which produced larges area of o/w microemulsion, were chosen for hemolysis study and particle size analysis. The result indicated that the formulations containing 2:1 weight ratio of Tween 20 to Imwitor 308 produced largest area of 0/w microemulsion existence. The particle size of microemulsion containing 2:1 weight ratio of Tween 20 to Imwitor 308 at 50% w/w surfactant mixture had the droplet size in the range of 10-13 nm and particle size tended to increase with increasing oil concentration in the system. The same trend was found for phase inversion temperature (PIT) in that the PIT increased with higher oil solubilization indicating that that the oil was located in the droplet core region. The microemulsions showed Newtonian flow and the viscosity was lower than their micelle formulations. The hemolysis study showed that the approximately the same concentration of 50% hemolysis (IC50)of the microemulsions investigated containing 5, 10 and 15% w/w were 0.33, 0.33 and 0.29 % w/v of surfactant mixture, repectively. The IC50 of correponding micelles was non-significantly lower than the microemulsions (p>0.05).