Azeco Cosmeceuticals

Question Can you recommend some formulation concepts?

Answer You asked me for more details on the formulation concepts that we apply/have applied on azelaic acid. As is valid for all actives used in personal care & cosmetic products, chemical-medical devices and pharmaceutical preparations applied on the skin: a product can only be effective when it will arrive at the place where it should exhibit its activity. In the case of azelaic acid a sincere complication is the solubility of azelaic acid: it is poorly soluble in the usual solvents, either hydrophilic or lipophilic. To be able to be subjected to transdermal transport azelaic acid must first be made soluble in the carrier: hydrophilic or lipophi - lic solvent preparations, emulsions or gels. Solubility of azelaic acid can be tuned using specific solvents such as ethoxydiglycol, ethoxytriglycol, esters isostearic acid, dimethyl esters of linear dicarboxylic acids (including azelaic acid) and some glycols. If solubility is achieved the solubilised/dissolved azelaic acid can be incorporated into a carrier that enables transdermal transport. There is no doubt whatsoever that ethoxydiglycol is superior to all other cosmetically suitable solvent, directly followed by ethoxytriglycol. It is also possible to solubilise azelaic acid by neutralisation with an organic base such as TRIS or neutralise with acetylglucosamine. In medical practice transdermal drug delivery has become very important since the 1990’s. Having said that the potential of trans- dermal transport is still largely untapped and has yet to fully achieve its position as an alternative to oral delivery or hypodermic injections. First-generation transdermal delivery systems, as we use it, face a gradual increase for the delivery of small hydrophilic or lipophilic, low-dose drugs. Second-generation delivery systems use chemical enhancers, ultrasound and iontophoresis to control de- livery rates in real time and provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, microdermabrasion and ultrasound. Microneedles are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. It is pretty obvious to state that second- and third-generation impact pharmaceutical applications and not personal & cosmetic products and medical devices. To enable transport of chemicals for each and any cell in the dermis a vast vascular network (capillaries) is present that also plays a role in wound healing and immune response. Capillary permeability is the rate- determining factor for the material exchange across the tissue/capillary barrier. Molecular transport is steered by physical driving forces such as concentration and pressure gradients, in other words diffusion & osmosis; diffusion is resisted by osmosis. This is described by the famous Kedem-Katchalsky equations (1958). Three types of capillaries are recognised in the human body: continuous, fenestrated and discontinuous capillaries. Continuous ca- pillaries, especially the ones in skin and skeletal muscle, are the least permeable. Continuous capillaries are also found in the cardiac muscle, in the brain and lungs. Fenestrae (windows) may be present as small circular openings, membrane-bounded circular disconti- nuities in the body of an endothelial cell. Discontinuous capillaries allow the passage of erythrocytes in and out of the systemic circulation through large gaps. Useful, to resist all kinds of riffraff. It is not surprising that these are found in the liver and in the lymphatic organs. Also in the dermal tissue, disconti- nuous capillaries are the majority, next to continuous capillaries.

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