Oil-in-water lecithin-based microemulsions as a potential delivery system for amphotericin B

In this work the structural features of microemulsions (MEs) containing the pharmaceutical biocompatible Soya phosphatidylcholine/Tween 20 (1:1) as surfactant (S), Captextrade mark 200 as oil phase (O), and phosphate buffer 10mM, pH 7.2 as aqueous phase (W) were studied. Systems obtained with different proportions of the components were described by pseudo-ternary phase diagrams in order to characterize the microemulsions studied here. MEs were prepared with and without the polyene antifungal drug amphotericin B (AmB). The maximum AmB incorporation into the ME system was dependent on both the oil phase and surfactant proportions with 6.80 and 5.7mg/mL in high contents, respectively. The incorporation of AmB into the ME systems significantly increased the profile of the droplet size of the ME for all ranges of surfactant proportions used in the formulations. The microstructures of the system were characterized by dynamic light scattering (DLS) and rheological behavior. The DLS results showed that the size of the oil droplets increases 4.6-fold when AmB is incorporated into the ME system. In all cases the increase in the proportion of the oil phase of the ME leads to a slight increase in the diameter of the oil droplets of the system. Furthermore, for both the AmB-loaded and AmB-unloaded MEs, the size of the oil droplets decrease significantly with the increase of the S proportion in the formulations, demonstrating the efficiency of the surfactant in stabilizing the ME. Depending on the ME composition, an anti-thixotropic behavior was found. The maximum increases of the consistency index caused by the increase of the oil phase of the ME were of 17- and 25-times for the drug-loaded and drug-unloaded MEs, respectively. However, the observed effect for the drug-loaded ME was about 4.6 times higher than that for the drug-unloaded one, demonstrating the strong effect of the drug on the rheological characteristics of the ME system. Therefore, it is possible to conclude that the investigated ME can be used as a very promising vehicle for AmB.     

Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine

Microemulsions (ME) containing soya phosphatidylcholine (SPC)/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the proportions between the components to form clear systems. The dynamic light scattering results showed that the size of the oil droplets decreases significantly with the ratio of surfactant/oil phase added to system. Depending on the composition ME system could exhibit a thixotropic behavior. The apparent viscosity increased 25- and 13-folds with cholesterol concentration for drug-free and drug-load ME, respectively. It was also verified that the octanol/aqueous buffer partition coefficient (KO/B) of doxorubicin (DOX) was pH dependent increasing abruptly above pH 6.0. It was possible to incorporate 2.24 mg/ml of DOX into ME. The incorporation of DOX in the ME systems increased the droplets size for all surfactant concentrations used in the system. The results suggest that DOX interacts with the microstructure of the ME at the studied pH increasing significantly the drug solubility. It was possible to conclude that the investigated ME can be a very promising vehicle as drug-carrier for administration of doxorubicin.     

Relationship between structural features and in vitro release of doxorubicin from biocompatible anionic microemulsion

In this work structural features of anionic microemulsions, containing the pharmaceutical biocompatible components soya phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as surfactant, cholesterol (CHO) as oil phase and aqueous buffer were studied. Microemulsions were formulated with and without the antitumor drug doxorubicin (DOX). The various microstructures characterized in the pseudo-ternary phase diagram were analyzed by polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD) as well as by their ability to incorporate and release DOX. The experimental results demonstrated a correlation between the composition, the structural features and drug delivery. It was found that at higher cholesterol contents, the crystallization of CHO polymorph phases changed the mobility of DOX molecules. Droplets were formed with short-range spatial correlation from a microemulsion (ME) with a low surfactant:oil ratio. More ordered structures with lamellar arrangements formed by the increasing of the CHO proportions in the formulation may be due to CHO crystallization. The in vitro release of DOX showed that the presence of a high content of crystalline CHO prolongs the release of DOX from ME. The retention of DOX in the internal oil phase of the ME may modulate the drug release for a prolonged time. These results clearly demonstrate the potential of ME as a drug-delivery system.     

Structural changes of biocompatible neutral microemulsions stabilized by mixed surfactant containing soya phosphatidylcholine and their relationship with doxorubicin release

Depending on the composition, the mixture of surfactant, oil and water, may form supramolecular aggregates with different structures which can significantly influence the drug release. In this work several microemulsion (ME) systems containing soya phosphatidylcholine (SPC) and eumulgin HRE40™ (EU) as surfactant, cholesterol (O) as oil phase, and ultra-pure water as an aqueous phase were studied. MEs with and without the antitumoral drug doxorubicin (DOX) were prepared. The microstructures of the systems were characterized by photon correlation spectroscopy, rheological behavior, polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD). The results reveal that the diameter of the oil droplets was dependent on the surfactant (S) amount added to formulations. The apparent viscosity was dependent on the O/S ratio. High O/S ratio leads to the crystallization of cholesterol polymorphs phases which restricts the mobility of the DOX molecules into the ME structure. Droplets with short-range spatial correlation were formed from the ME with the low O/S ratio. The increase of the cholesterol fraction in the O/S mixture leads to the formation of ordered structures with lamellar arrangements. These different structural organizations directly influenced the drug release profiles. The in vitro release assay showed that the increase of the O/S ratio in the formulations inhibited the constant rate of DOX release. Since the DOX release ratio was directly dependent on the ratio of O/S following an exponential decay profile, this feature can be used to control the DOX release from the ME formulations.