Azeco Cosmeceuticals

Solubility

3. Question: Should we consider 10-15 % Azelaic acid in Propanediol?

Answer: A base formulation can be generated by dissolution of Azelaic acid in propanediol (Zemea, ex.Dupont), chemically identified as 1,3-propanediol. The solution of Azelaic acid in propanediol does not require preservation and may be thickened using 3-4% hydroxy propylcellulose (HPC; Ashland). To the obtained gel other active ingredients can be added, provided the additive is miscible with the Azelaic acid/propanediol gel. That is the case for hydrophilic extracts, but also oil-in-water emulsions. The solubility of Azelaic acid in propanediol is relatively high. Solutions of 10-15% are frequently used. The maximum solubility of Azelaic acid in propanediol is not determined and would need to be researched. Note that gelation of propanediol with HPC is a tedious process. 4. Question: Is the solubilty of Azelaic acid in propanediol 1,3 similar to that of propylene gly col? We are planning to experiment with solubilizing in propanediol then suspending in sclero tium gum adjusted to 3.8 pH (as part of a combination AHA formulation). Would this adversely affect bio-availability and/or risk crystallization? Answer: 1. The solubility of Azelaic acid in 1,2-propylene glycol (INCI: Propylene Glycol) is comparable with 1,3-propylene glycol (INCI: Propa nediol). I understand where your client s coming from as 1,2- propylene glycol is from petrochemical origin and 1,3-propylene glycol is obtained by fermentation of corn sugar and has an EcoCert/Cosmos approval. Having said that, the solubility of Azelaic acid in both solvents is rather limited indeed. The solubility of Azelaic acid in both solvents can be greatly increased as follows: a. Add ethoxydiglycol or ethoxytriglycol to the glycols to further increase the solubility. Ethoxydiglycol is limited in concentration for personal care & cosmetics by the EU Legislator; ethoxy triglycol can be used freely without concentration limitations. For the USA the FDA has not put any constraints to both solvents. 2. Azelaic acid is well tolerated by sclerotium gum (Alban Muller) and vice versa. While working in an anhydrous environment there is no concern for the pH of the system. Having said that, quantitative data on the acid/base behavior in non-aqueous solvents have not been published. When following the instructions as laid down in §1 the risk of crystallization will be minimized (but not zero!), to be confirmed by a shelf life study. Usually crystallization phenomena pop up already after a few days. 5. Question: We have tried another source of Azelaic acid (not Azepur99®) and experienced some problems with crystallization for an skin prone to acne application. Now we are going to try the Azepur99® sample. Solvent used is PEG-400, which other solvents do you recom mend? Answer: It is better to add also propylen glycol, butylen glycol or other low molecular weight glycols. For more information can be found on the Essential Guide chapter 6 page 28. 6. Question: Is Azepur99® is soluble in glycerin, 1.3-Butylene Glycol or Propanediol? b. Azelaic acid can properly be dissolved in these glycols using chitosan in a (semi)-stoichiometric quantity. Reference is made to your booklet and the publication in SPC.

Answer: Yes in a mixture 50/50 of 1,3 butylene glycol/propanediol it is possible to solubilise up to 10% of Azelaic acid.

Mussenberg 1 • 6049 GZ Herten • The Netherlands

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