Dissolution, micelles

The thermodynamic equilibria of surfactant molecules in hydrocarbon solutions involve four fundamental processes dissolution, micellization, solubilization and interfacial processes, see Fig. 3.3 (Kertes and Gutman, 1976 Kon-no, 1993 Moroi, 1992). 

Recent developments m calorimetry have focused primarily on the calorimetry of biochemical systems, with the study of complex systems such as micelles, protems and lipids using microcalorimeters. Over the last 20 years microcalorimeters of various types including flow, titration, dilution, perfiision calorimeters and calorimeters used for the study of the dissolution of gases, liquids and solids have been developed. A more recent development is pressure-controlled scamiing calorimetry [26] where the thennal effects resulting from varying the pressure on a system either step-wise or continuously is studied. 

Studies described in earlier chapters used cellular automata dynamics to model the hydrophobic effect and other solution phenomena such as dissolution, diffusion, micelle formation, and immiscible solvent demixing. In this section we describe several cellular automata models of the influence of the hydropathic state of a surface on water and on solute concentration in an aqueous solution. We first examine the effect of the surface hydropathic state on the accumulation of water near the surface. A second example models the effect of surface hydropathic state on the rate and accumulation of water flowing through a tube. A final example shows the effect of the surface on the concentration of solute molecules within an aqueous solution. 

The structure of these globular aggregates is characterized by a micellar core formed by the hydrophilic heads of the surfactant molecules and a surrounding hydrophobic layer constituted by their opportunely arranged alkyl chains whereas their dynamics are characterized by conformational motions of heads and alkyl chains, frequent exchange of surfactant monomers between bulk solvent and micelle, and structural collapse of the aggregate leading to its dissolution, and vice versa [2-7]. 

Certain surface-active compounds [499], when dissolved in water under conditions of saturation, form self-associated aggregates [39,486-488] or micelles [39,485], which can interfere with the determination of the true aqueous solubility and the pKa of the compound. When the compounds are very sparingly soluble in water, additives can be used to enhance the rate of dissolution [494,495], One can consider DMSO used in this sense. However, the presence of these solvents can in some cases interfere with the determination of the true aqueous solubility. If measurements are done in the presence of simple surfactants [500], bile salts [501], complexing agents such as cyclodextrins [489 191,493], or ion-pair-forming counterions [492], extensive considerations need to be applied in attempting to extract the true aqueous solubility from the data. Such corrective measures are described below. 

Solubility and dissolution are processes that take place in the gastric and the luminal fluids, not on the surface of epithelial cells. Measurement of solubility ideally needs to take place at pH 1.7 (stomach) and pH 5-8 (small intestinal tract). Ideally, the screen media should resemble intestinal fluids and contain bile acid-lecithin mixed micelles. Fast and reliable techniques for assessing solubility in... 

P Singh, S Desai, D Flanagan, A Simonelli, W Higuchi. Mechanistic study of the influence of micelle solubilization and hydrodynamic factors on the dissolution rate of solid drugs. J Pharm Sci 57 959, 1968. 

The basic mechanism for surfactants to enhance solubility and dissolution is the ability of surface-active molecules to aggregate and form micelles [35], While the mathematical models used to describe surfactant-enhanced dissolution may differ, they all incorporate micellar transport. The basic assumption underlying micelle-facilitated transport is that no enhanced dissolution takes place below the critical micelle concentration of the surfactant solution. This assumption is debatable, since surfactant molecules below the critical micelle concentration may improve the wetting of solids by reducing the surface energy. 

Figure 7 Stagnant film model (top) and reaction plane model (bottom) for micelle-facilitated dissolution.

Mathematical approaches used to describe micelle-facilitated dissolution include film equilibrium and reaction plane models. The film equilibrium model assumes simultaneous diffusive transport of the drug and micelle in equilibrium within a common stagnant film at the surface of the solid as shown in Figure 7. The reaction plane approach has also been applied to micelle-facilitated dissolution and has the advantage of including a convective component in the transport analysis. While both models adequately predict micelle-facilitated dissolution, the scientific community perceives the film equilibrium model to be more mathematically tractable, so this model has found greater use. 

The kinetic scheme used to describe micelle-facilitated dissolution is... 

A method used to describe the enhanced dissolution rate following micelle-facilitated dissolution is to compare the dissolution of the drug in the surfactant solution to that of the dissolution rate in water this is often termed the reaction factor method. The reaction factor, ( vM, which is the total flux of the micelle-solubilized solute plus the free solute divided by the flux of the free solute, is given by... 

The reaction plane model with heterogeneous reactions was discussed at length for acid-base reactions in the previous section. The same modeling technique, of confining the reactions to planes, can be applied to micelle-facilitated dissolution. As with the acid-base model, one starts with a one-dimensional steady-state equation for mass transfer that includes diffusion, convection, and reaction. This equation is then applied to the individual species i, i.e., the solute, s, the micelle, m, and the drug-loaded micelle, sm, to yield... 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

LJ Naylor, V Bakatselou, JB Dressman. Comparison of the mechanism of dissolution of hydrocortisone in simple and mixed micelle systems. Pharm Res 10 865-870, 1993. 

Micelles forming above the c.m.c. incorporate hydrophobic molecules in addition to those dissolved in the aqueous phase, which results in apparently increased aqueous concentrations. It has to be noted, however, that a micelle-solubilised chemical is not truly water-dissolved, and, as a consequence, is differently bioavailable than a water-dissolved chemical. The bioavailability of hydrophobic organic compounds was, for instance, reduced by the addition of surfactant micelles when no excess separate phase compound was present and water-dissolved molecules became solubilised by the micelles [69], In these experiments, bacterial uptake rates were a function of the truly water-dissolved substrate concentration. It seems therefore that micellar solubilisation increases bioavailability only when it transfers additional separate phase substrate into the aqueous phase, e.g. by increasing the rates of desorption or dissolution, and when micelle-solubilised substrate is efficiently transferred to the microorganisms. Theoretically, this transfer can occur exclusively via the water phase, involving release of substrate molecules from micelles, molecular diffusion through the aqueous phase and microbial uptake of water-dissolved molecules. This was obviously the case, when bacterial uptake rates of naphthalene and phenanthrene responded directly to micelle-mediated lowered truly water-dissolved concentrations of these chemicals [69]. These authors concluded from their experiments that micellar naphthalene and phenanthrene had to leave the micellar phase and diffuse through the water phase to become... 

SANS has been recently used to study problems related to micelle preparation and kinetics, as reported by Bates and coworkers who have used time-resolved SANS to study molecular exchange and micelle equilibration for PEO-PB diblocks in water [71]. The authors have shown that the micellar structures initially formed upon dissolution were completely locked in up to 8 d after preparation. Fluorometry and DLS have also been used to monitor micelle equilibration [72],... 

Performance Indices Quality Factors Optimum E1LB Critical micelle concentration (CMC) Soil solubilization capacity Krafft point (ionic surfactants only) Cloud point (nonionic surfactants only) Viscosity Calcium binding capacity Surface tension reduction at CMC Dissolution time Material and/or structural attributes... 

Balakrishnan A, Rege BG, Amidon GL, Polli JE (2004) Surfactant-mediated dissolution Contribution of solubility enhancement and relatively low micelle diffusivity. J. Pharm. Sci. 93 2064—2075. 

Surface-active agents used as adjuvants in pharmaceutical preparations to improve drug dissolution may affect the stability of /3-lactams. Thus, the presence of micelles of cetyl(trimethyl)ammonium bromide (CTAB) enhanced up to 50-fold the rate of alkaline hydrolysis of penicillins [140]. In the case of cephalosporins, micelle-promoted catalysis of the intramolecular degradation process (see Sect 5.2.2) was also observed [85][141], It has been proposed that the negatively charged penicillins and cephalosporins are attracted by the cationic micelles. This attraction increases substrate concentration in the micellar phase, in turn accelerating the rate of HO- ion attack. Ion exchange at the micellar surface and electrostatic stabilization of the transition state may also contribute to the increased rate [142][143],... 

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