Salicylic acid solubilization

Reverchon E, Donsi G, Gorgoglione D. Salicylic acid solubilization in supercritical CO2 and its micronization by RESS. J Supercrit Fluids 1993 6 241-248. Subra P, Boissinot P, Benzaghou S. Precipitation of pure and mixed caffeine and anthracene by rapid expansion of supercritical solutions, Proceedings of the 5th meeting on Supercritical Fluids. Vol. 1. Perrut M, Subra P, ed. 23-25 March, Nice, France, 1998 307-312. 

Reverchon, E., Donsl, G. and Gorgoglione, D. (1993) Salicylic Acid Solubilization in Supercritical CO2 and Its Micronization by RESS,y. Supercrit. Fluids 6,241-248. 

Haapakka and Kankare have studied this phenomenon and used it to determine various analytes that are active at the electrode surface [44-46], Some metal ions have been shown to catalyze ECL at oxide-covered aluminum electrodes during the reduction of hydrogen peroxide in particular. These include mercu-ry(I), mercury(II), copper(II), silver , and thallium , the latter determined to a detection limit of <10 10 M. The emission is enhanced by organic compounds that are themselves fluorescent or that form fluorescent chelates with the aluminum ion. Both salicylic acid and micelle solubilized polyaromatic hydrocarbons have been determined in this way to a limit of detection in the order of 10 8M. 

Salicylic acid has been extensively used in dermatologic therapy as a keratolytic agent. The mechanism by which it produces its keratolytic and other therapeutic effects is poorly understood. The drug may solubilize cell surface proteins that keep the stratum corneum intact, thereby resulting in desquamation of keratotic debris. Salicylic acid is keratolytic in concentrations of 3-6%. In concentrations greater than 6%, it can be destructive to tissues. 

Micellar solutions of detergents such a sulfonates, phenolates and salicylates enhance the solubilizing properties of succinimide additives. For small concentrations of about 0.25% w/w sulfonate and 2.8% succinimide, a synergistic effect is observed, but for high sulfonate concentrations, the quantity of acid solubilized is less than that observed for succinimide alone (Bradley and Jaycock, 1972). A different mechanism exists for the solubilization of those weak acids and for strong acids. The different interaction between the amine groups in the polar head of a succinimide micelle and a weak acid (WH), and for a strong acid (SH), indicates that the weak acid is much better solubilized as ... 

Bradford Particle Design patented another way to perform the SEDS. In this method, nitrogen was the antisolvent, while the substrate to be micronized was solubilized in CO2. Salicylic acid was processed by means of this approach (140) Table 4 provides additional examples (15,16,132-134,136, 137,141-156). 

Complexation. It has been well established in the literature that complexation is an effective way to solubilize hydrophobic compounds. Nicotinimide is known to complex with aromatic drugs through tt donor-7r acceptor interaction (101). Similar tt-tt interaction also occurs between salts of benzoic acid or salicylic acid and drugs containing aromatic rings such as caffeine (102).Obviously, aromaticity is an important factor in this type of complexation. Unfortunately, from a safety perspective the use of these types of complex-ing agents for products is not really very viable. 

Salicylic acid is a P-hydroxy acid that is thought to function through solubilization of intercellular cement, again reducing comeocyte adhesion. It appears to eliminate the stratum comeum layer by layer from the outermost level downward. This contrasts with the a-hydroxy acids, which preferentially diminish cellular cohesion between the cor-neocytes at the lowest levels of the stratum comeum. 

Beilstein Handbook Reference) Benzoic acid, 2-hydroxy-, 2-ethylhexyl eslen BRN 2730664 Dermoblock OS EINECS 204-263-4 Ethyl hexyl salicylate 2-Ethylhexyl salicylate Ethylhexyl salicylate 2-Ethylhexyl 2-hydroxybenzoate Neo Heliopan OS NSC 46151 Octisalate Octyl salicylate Salicylic acid, 2-ethylhexyl ester Sunarome 0 Sunarome WMO USAF DO-11 Uvinul 0-18 WMO. UV-B absorber for cosmetic applicabons, waterproof sunscreens solubilizer for oxybenzone. Solid bp2i = 189-190° d = 1.014. Akzo Chemie BASF Corp. Haarmann Reimer GmbH. 

Direct introduction of a solubilizing function can be achieved by carboxylation and by sulfonation. The historical example of carboxylation is the Kolbe synthesis of salicylic acid. Sulfonation was employed to solubilize guaiacol, camphor and 7-chloro-8-hydroxyquinoline (Fig. 36.1). 

Figure 11.12 Influence of micellar solubilization on co-crystal solubility and CSC for two co-crystals of carbamazepine with different stoichiometries and aqueous solubilities at 25 °C. The dashed line shows the SLS concentration at the CSC, where co-crystal and drug are thermo-d5mamically stable. The solid lines represent predicted co-crystal and drug solubilities according to equations (11.30) and (11.34) for a 1 1 cocrystal, carbamazepine-salicylic acid (CBZ-SLQ. The equation for a 2 1 co-crystal, carbamazepine-succinic acid (CBZ-SUC) has been presented in the literature. ...

The influence of micellar solubilization on co-crystal eutectic points is presented in Table 11.2 for carbamazepine-salicylic acid (CBZ-SLC) in aqueous media. Addition of surfactant reverses the co-former to drug molar concentration ratios at the eutectic. In the absence of surfactant, [SLC]e > [CBZ]e , indicating that the co-crystal requires excess co-former to be at equilibrium with pure drug. This situation is reversed in 35 mM (1%) SLS solution, where [CBZ]eu > [SLC]eu demonstrating that there is a CSC at SLS concentrations below 1 %. 

Table 6.24 Effect of polysorbate 20 on the solubilizing power of polysorbate 80 on salicylic acid...

The presence of polysorbates 20 and 80 decreases the transfer rate constant of salicylic acid across cellophane membranes at low pH [59]. Ionized salicylic acid does not partition into the micelles and thus at pH values above 5 polysorbate has little effect on permeation as cellophane membranes with small pore size are regarded to be impermeable to surfactant micelles [60]. The effect of solubilization is to reduce the concentration gradient of the solute across the membrane. Taking into account distribution of drug between the aqueous and micellar phases, Juni et al. [61] have derived an equation to describe the permeation profiles of drugs from systems containing micelles. A simplified model is shown in Fig. 7.19. 

When aqueous diffusional barriers on each side of the lipoidal membrane are included, Pick s law does not fully hold in this case of protonation of weak bases. The transfer of amidopyrine and salicylic acid through an organic liquid obeys the theoretical equation proposed5. The formation of complexes can modify the rate of transfer of drugs through such barriers and demand modification of the diffusional equations . When micron-sized emulsion droplets act as sinks for drug, equations were derived for micellar solubilization to take into account the possible effects of an ... 

Aqueous solutions of certain salts, such as those of benzoic, salicylic, benzene-sulfonic, naphthoic, and various hydroaromatic acids, possess the power of dissolving certain substances otherwise not soluble in water. These substances, known as hydrotropes, are structurally similar to surfactants in that they have hydrophilic and hydrophobic moieties in the same molecule, but the alkyl chain is shorter. A few typical hydrotropes are listed in Figure 26.8. When solubilization... 

Caprylic/capric triglyceride PEG-4 esters Diisopropyl sebacate Isopropyl isostearate PEG-4 ditallate PEG-40 sorbitan peroleate PEG-20 sorbitan triisostearate PEG-100 stearate Stearyl stearate solubilizer, benzophenone Cetyl ricinoleate solubilizer, benzophenone-3 Dioctyl maleate Methyl acetyl ricinoleate Octyl palmitate Octyl salicylate solubilizer, biocides Cocamidopropyl hydroxysultaine N,N-Dimethyl-N-lauric acid-amidopropyl-N-(3-sulfopropyl)-ammonium betaine N,N-Dimethyl-N-myristyl-N-(3-sulfopropyl)-ammonium betaine N,N-Dimethyl-N-palmityl-N-(3-sulfopropyl)-ammonium betaine N,N-Dimethyl-N-stearyl-N-(3-sulfopropyl)-ammonium betaine... 

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