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We attempted to improve the solubility of poorly water-soluble drugs by preparing drug-loaded polyvinyl alcohol (PVA) nanofibers as a solid dispersion system via emulsion electrospinning. Probucol (PBC), a poorly water-soluble drug, was used as a model drug. Nanofibers were electrospun using an oil/water (o/w) emulsion consisting of PBC dissolved in an immiscible solvent, such as ethyl acetate, and an aqueous PVA phase. PBC-containing PVA nanofibers with diameters ranging from 300 to 600 nm were obtained by electrospinning from o/w emulsions. The physical properties of the nanofibers were affected by the degrees of polymerization and hydrolysis of the PVA grades. In PVA nanofibers prepared without a surfactant, PBC existed in an amorphous state, and the dissolution of PBC was greatly improved. PBC dissolution was lower in PVA nanofibers with 30% PBC content compared to those with 11% or 20% PBC. In PVA nanofibers prepared using the surfactant P80 as an emulsifier, PBC was partially crystallized; however, the PBC was homogenously dispersed, and dissolution was improved, even in PVA nanofibers containing 30% PBC. PVA nanofibers produced by o/w emulsion electrospinning were demonstrated to be suitable solid dispersion systems enabling robust controlled release of poorly water-soluble drugs.

The phase diagrams, i.e., the pressure—temperature—composition diagrams of each system tetra-, penta-, and hexaoxyethylene dodecyl ether (C 12 E 4 , C 12 E 5 , and C 12 E 6 ,respectively) vs water, have been determined by the use of the observation that the transmittance of the solution changes sharply with the change of the dissolved state of the solute. The temperature—pressure phase diagrams involve the regions of the micellar solution, the liquid surfactant phase + water phase, the hydrated solid + water phase, and the liquid crystal + water phase. The cloud temperature increased and its increasing rate became smaller with increasing pressure. By considering that the cloud temperature—composition curve is a liquid—liquid mutual solubility curve and the idea of “associated solution” of Prigogine and Defay, we derived the thermodynamic quantities (enthalpy, entropy, and volume) accompanied by the separation of the liquid surfactant phase from the water phase above the cloud temperature for the C 12 E 5 —water system. The enthalpy and entropy changes were positive and depended little on pressure, while the volume change was positive and decreased, tending to zero, with the pressure up to 300 MPa. This suggests that hydrophobic bonding as well as the partial dehydration of oxyethylene groups of surfactant contribute to the separation of the liquid surfactant phase from the water phase. In the composition—pressure diagram close to the regions of the micellar solution and the hydrated solid + water phase for the C 12 E 5 —water system, a sudden increase in the solubility of surfactant at a certain pressure was found with decreasing pressure and at constant temperature, which corresponds to the Krafft phenomenon and can be attributed to the effective dissolution of surfactant as a micellar form in water.

In order to determine the pressure dependence of the maximum additive concentration (MAC) of octane or decane in the aqueous solution of octaoxyethylene dodecyl ether (C12E8, 1% w/w), the pressure dependence of the cloud points and that of the temperatures of the solubilization limit for the solutions containing various concentrations of the alkane were determined by the change in transmittance of the solution. The MAC monotonously decreased with increasing pressure up to 300 MPa at a constant temperature below the cloud point. This relation is different from that obtained for the solubilized systems in which β-phenylethyl alcohols are solubilized in aqueous solutions of cetyltrimethylammonium bromide: the MAC versus pressure relation with a maximum near 100 MPa [Part I, J. Colloid Interface Sci.94, 348 (1983)]. The difference may be associated with the differences of the incorporation sites of solubilizates in micelles and of their solubility in the bulk (water); i.e., alkanes are incorporated into the micelle core and dissolve very little in water, while β-phenylethyl alcohols penetrate into the palisade layer close to the micelle surface and dissolve slightly in water. The pressure dependence of the MAC was analyzed by means of the pseudophase model for micelles. The conventional pseudophase model in which the Laplace pressure inside a micelle is not allowed failed to explain the MAC-pressure relation; however, the corpuscular pseudophase model, taking into account the Laplace pressure, could quantitatively explain the relation well. It can therefore be concluded that the Laplace pressure obviously contributes to the micellar solubilization of the alkanes.