We have investigated the effect of alcohols and other additives on the binary phase diagram water-C12E5. In particular, we have located the dilute lamellar L" phase and the L3 phase as function of additive concentration on the temperature scale.In the L" phase undulations stabilize bilayer membranes at distances on the order of hundred nanometers. We have determined their repeat distance quantitatively by light scattering. By addition of medium-chain alcohols, the projected area of the undulating membranes was found to increase drastically. We quantitatively determined the fraction of alcohol molecules dissolved in the membranes by 2H NMR using deuterated alcohols. The longer the hydrocarbon chain of the alcohols, the stronger the partitioning of the alcohols into the membranes. From our experiments we conclude that the bilayers act as a two-dimensional phase into which the medium-chain alcohols preferentially dissolve, apparently because of the favorable polarity gradient of the films. This latter conclusion arises from the surfactant-like order parameter profile observed by 2H NMR for the alcohols. The effect of adding salt, increasing the hydrocarbon chain length of either surfactant or alcohol, as well as reducing the number of ethylene oxide units of the surfactant is, in each case, to render the bilayers more hydrophobic. We discuss the effects in terms of the geometric properties of the molecules and bending properties of the membranes.

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The release of timolol maleate, a drug for treatment of glaucoma, from cubic liquid crystals consisting of charged and uncharged lipids was investigated in vitro. It was shown that the release of drug was dependent on the ionic strength of the receptor medium and the relative amount of a charged phospholipid in the cubic phase. In the absence of charged lipids, the release of timolol was complete, irrespective of the medium used, i.e. distilled water or saline solution. In the presence of a negatively charged phospholipid, diacylphosphatidylglycerol, the release of drug from the cubic phase was incomplete when distilled water was the receptor medium. The residual drug was dependent on the amount of charged lipid in the cubic phase. In saline solution, on the other hand, all of the drug was released. The results are interpreted as an effect of electrostatic attraction between the positively charged drug with the negatively charged bilayer surface, which is screened in the presence of saline. The possible influence of the cubic geometry is discussed as well. This work shows that lipids offer many possibilities in the formulation of sustained drug release systems.

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