Azeco Cosmeceuticals

Solubility

1. Question: How to improve the solubility of Azelaic acid?

Answer: Azelaic acid is poorly soluble in water, as described earlier by Brand-Garnys & Brand. The monosodium & disodium slats are slightly better soluble but as a result the pH of these solutions is alkaline, frequently a disadvantage. Mather & Stahl (WO 1996.039119) des cribed several combinations of solvent, frequently glycols that enable to properly dissolve Azelaic acid.

Example 1. 40 parts ethoxydiglycol

3 parts diisopropyl adipate 1-10% Azelaic acid Mix & stir until a clear solution has been obtained.

Example 2. 40 parts dipropylene glycol 1-10% Azelaic acid

Mix & stir while heating to 60°C until a clear solution has been obtained. Dipropylene glycol and ethoxydiglycol are excellent solvent systems for Azelaic acid. It is recommended to further dilute the solutions of example 1 and example 2 with other glycols, more par ticularly propanediol (1,3-dihydroxypropane), pentylene glycol (1,2- dihydroxypentane), glycerol, ethoxylated glycerol (glycereth-12, 18,20 & 26) and similar polyols. The solutions enable to dissolve up to 25% Azelaic acid, and may function as the basis of serum preparations for use in personal care & cosmetic preparations as well as medical device, as well as a starting product for e.g. emulsion & gel preparations.

For more information see the Azelaic acid essential guide, Chapter 6, page 28: Solubility of Azelaic acid.

2. Question: How to dissolve Azelaic acid?

Answer: The limited solubility of Azelaic acid in aqueous conditions requires some creativity. There are several methods to incorporate Azelaic acid in a final formulation using a premix. The most straight forward approach is to dissolve Azelaic acid in ethanol or isopropanol. For many preparations these alcohols are not the most preferred substances. In that case a suitable diol will do the job. We have tested propanediol (Zemea®; Dupont), as well as 1,3-butylene glycol and pentylene glycol. Pentylene offers the advantage that it also gives a massive microbiological protection. Pentylene glycol is available from petrochemical origin (Symrise, Minasolve), but also from vegetable origin, obtained by hydroge nation of furfuraldehyde (from wood processing; Minacare Pentiol Green/Minasolve). Also glycerin and glycerin/water mixtures are suitable solvent systems; the maximum concentration water in this solvent mixture are not properly defined and not reported in the literature. A second, but far more expensive option is to dissolve Azelaic acid is a mixture of phosphatidylcholine & isopropyl palmitate. In this case a premix is made of Azelaic acid in an aqueous glycerin solution. This procedure is only recommended when dissolution in glycols of glycerin/water mixtures fails.

Mussenberg 1 • 6049 GZ Herten • The Netherlands

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