LI phases

The screening of permeability coefficients for orally available drugs in the LI phase can be made with the intention to ... 

It bears repeating that the values are effective diffusivities and that, in fact, diffusivity is a function of surfactant concentration, as shown by interferometry for the Li phase of Ci2(EO)5 [9]. For the anisotropic phases diffusivity is also a function of orientation, and Dej depends on the number and orientation of domains of the phase as formed during dissolution. Thus, the value shown in Table 1 for DgHi of Ci2(EO)6 is intermediate between the diffusivities parallel and perpendicular to the rodlike micelles measured in fully oriented samples of the hexagonal phase Hi for this surfactant [26]. 

Since their effective diffusivities are of the same magnitude as those of micellar solutions, the hquid crystalUne phases, though viscous, do not significantly hinder surfactant dissolution for these rather hydrophihc surfactants. Indeed, a drop of Ci2(EO)6 having Ro = 78 pm dissolved completely in only 16 s at 30 °C. Rapid dissolution is favored because free energy decreases as the surfactant is transferred from the Hquid surfactant phase L2 to liquid crystals) to aqueous micellar solution and the aggregate shape approaches that of a dilute Li phase, where its free energy is minimized at this temperature. 

Example 13.2. It is instructive to relate the film pressure to a three-dimensional pressure (Fig. 13.5). On the barrier of length l the film exerts a force nl. In the three-dimensional case we estimate the force from the pressure P which acts upon a surface Id, where d is the thickness of the monolayer. This force is Pld. If the forces are set equal, we obtain P = Tt/d. Typical values for a monolayer in the Li phase arc d 1 nm and 7r = 10-3 N/m. Then we estimate a three-dimensional pressure of P = 106 N/m2 = 10 atm. 

An immediate consequence of eq. 4.3 is that the surfactant parameter must equal and b for surfactant solutions to form ordinary micelles (called the "Li phase" in the trade) and cylinders (Hj pheise) respectively - regardless of the surfactant concentration. 

Further adsorption of Li beyond 1/2 ML coverage at room temperature causes a gradual decrease in intensity of the fractional-order spots in the LEED pattern of the c(2 X 2)—Li phase and some increase in background intensity. However,... 

Fig. 15. Hard-sphere scale model of the structure of the Al(100)-c(2 x 2)-Li phase formed by adsorption of 1/2 ML Li at room temperature, a) top view, showing the unit cell, b) side view, shown as a central projection on the [010] plane through the dashed line in a).

As shown in Table 19, calculations [88] using the full-potential linearised augmented plane wave (FLAPW) method for the Al(lOO)—c(2 x 2)—Li phase formed by adsorption of 0.5 ML Li at room temperature con rm quantitatively the results of the LEED analysis described in Sec. 4.3 where, as shown in Fig. 15, Li was found to adsorb in a four-fold, substitutional site. 

Comparison of theory and experiment for the surface geometry of the Al(lOO)—c(2 x 2)—Li phase with Li atoms in substitutional sites. The interlayer spacings between the / th and y th layers are denoted dij (A), where d(, (A) is the Li-Al spacing. The calculated adsorption energy is denoted Bad (eV atom" ). 

The Cu 100 -p(2xl)-Li phase is imperfect at room temperature with the superstructure LEED beams being streaked. LEED I(V) analysis, indicates formation of a missing row type reconstruction in which every second Cu row along the [Oil] (or [Oil] in the 90° rotated domain) directions is removed [92,94,95], Lithium atoms are assumed to occupy the missing rows forming a CuxLij.x surface alloy as illustrated in figure 8. 

The effects of adding n-pentanol or n-hexanol to the Li phase were studied in the following manner. To systems containing 9.9, 14.7, or 19.4 wt% aqueous SLS was added MMA in 25, 50, or 67% excess of that which would saturate the system (Lj phase boundary). Alcohol was then added to the resulting two-phase system and the minimum alcohol content necessary to produce a microemulsion determined. 

It has been established that the behavior of a hydrocarbon in microemulsion formulations can be characterized by its Equivalent Alkane Carbon Number (EACN) (22). This is the number of methylene and methyl carbons making up the molecule. The EACN for MMA should be two and has been determined as such in this laboratory. It is interesting that this correlation seems to apply also to the measured free energies of transfer. This suggests that this previously empirical correlation has a theoretical basis in thermodynamics. Further, in the Li phase, up to a MMA concentration of at least 0.5 M, the free energy of transfer is constant, indicating that the micelle structure is probably not too much different from that at very low MMA concentrations. 

From these results, it is obvious that the extensive Li phase in the water, SLS and MMA phase diagram is a result of MMA possessing a rather favorable water interaction. It is just this interaction that enables MMA to come to the interface and plug the gaps in the expanding surface film. This phenomenon is probably not as important in systems containing less hydrophilic oils. 

In addition to vapor (V), high-density liquid (L2), or low-density liquid (Li) phase behavior, reservoir fluids, oils, and other organic fluids exhibit a variety of multiphase behaviors and critical phenomena as noted in Fig. 1. These include liquid-vapor (LiV or L2V), liquid-liquid (L1L2), and liquid-liquid-vapor (L1L2V) phase behavior and associated critical phenomena. 

At higher surfactant concentrations the ratio of alcohol to surfactant molecules does not exceed 2 at the phase boundary, and it appears that the alcohols promote structural changes of the micelles, for example from spherical to rodlike or ellipsoidal structures. This structural change is dependent both on the surfactant concentration and on the amount of solute, which is apparent from the study carried out by Backlund and co-workers who mapped the whole LI-phase of the SDS-1-hexanol and C gBr-l-hexanol systems demonstrating regions in the phase diagram relating to spherical micelles, spherical swollen micelles, and rodlike micelles. 

The solubility of n-decanol in the LI phase is also important (up to 12% at the end of the LI phase). The LI phase is accountable for the observation of oil-inwater (o/w) microemulsions. The La domain, generally located in the middle of the diagram, points toward the water side for a critical surfactant-to-cosurfactant ratio. (A 1 2 sodium octanoate to n-decanol ratio leads to a lamellar phase with as little as 17% surfactant-cosurfactant mixture.) In some cases, such as for octyl trimethylammonium bromide (OTAB)-hexanol-water, the lamellar phase already exists for 3% hexanol + 3% OTAB ... 

It was stated earlier that the solubility of decane in the LI phase is almost zero. For a well-defined surfactant-to-cosurfactant ratio, very large quantities of decane (or any hydrocarbon) can be solubilized in the LI phase. A thin, snake-like singlephase domain develops toward the oil vertex of the phase diagram (Figure 3.10). This phase can be regarded as amphiphile micelles swollen with oil. 

By the end of 2002, the Aventis project portfolio was transformed. Of the 139 projects in the LI phase, the kinase and GPCR target families each contributed 19%, the protease and ion channels/transporters about 8% each. For projects in the candidate identification phase, GPCR, kinase, and protease target families each contributed about 20% of the compounds and ion channels/transporters about 12% of the compounds in the portfolio. 

---