FORMULATING
the surface of the skin cell where it will slowly diffuse into the cell.
Absorption – Where an active ingredient directly passes unaided across the skin or cell membrane where it begins to work. This is the basic technology for percutaneous absorption, and probably the major pathway that is used by cosmetic chemists.
Formulation
The basic structure of an emulsion is well known but the selection of emulsifiers and lately the selection of the emollient are undergoing much closer scrutiny.
Emulsifiers Originally, soap was the first emulsifier used. Sodium stearate however has some major drawbacks. It is somewhat insoluble, actually causing the product to gel at levels above 5% (note: 8% is used to solidify products such as deodorant sticks). It has low oil carrying capacity and it is only effective in alkaline conditions (otherwise it hydrolyses back to the fatty acid). Later, triethanolamine stearate was used proving to be more soluble and hence higher levels could be used (also increasing the oil carrying capacity). The pH was also lower but still in the mild alkaline region for best stability. With the advent of synthetic surfactants in the 1950s, sodium lauryl sulfate was used (Aqueous Cream BP) although the use of sodium lauryl sulfate provides such stable emulsions that they do not absorb into the skin readily. They are best used for cleansers or sunscreens that you do want to absorb into skin. pH was also lower with an ideal range of 5.5 to 8, lower than 5.5 hydrolysis occurs with loss of emulsification power. Cationics have been used to a minor extent, particularly where the additional benefits of antiseptic efficacy is desired. These have not had widespread acceptance due to their poor stability profile, cationic surfactants being poor emulsifiers. The BP lists Cetrimide Cream BP. Still, they are substantive to skin and may assist in holding the active ingredient on the skin to aid absorption. Later the use of cetomacrogol 1000 (or now called ceteareth-20) or ICI’s extensive development of ethoxylated fatty alcohols and sorbitan derivatives allowed nonionic emulsions to be formed having a wide range of pH values, excellent penetration characteristics and a vast range of applications (from water-in-oil emulsions to wetting agents to oil-in-water emulsions to solubilised oil phases depending on the Hydrophilic-Lipophilic Balance (HLB) chosen). The BP contains formulations for Cetomacrogol Cream BP and Sorbolene Cream BP.
The use of a correct emulsifier for skin lightening products depends both on the active ingredient used for skin lightening and on the type and quantity of emollients used. The only time the selection of a correct emulsifier is of major concern is when there is a compatibility concern. For example, when using ascorbic acid or kojic acid, a low pH is required for maximum chemical stability of the drug. At low pHs there are certain emulsifiers, such as sodium lauryl sulfate, that are not stable. In these cases an acid stable emulsifier should be selected.
Emollients
Again early emulsions, reported in such august publications as the British Parmacopoeia, used an emollient phase based on paraffin liquid (or mineral oil), petrolatum and paraffin wax. These are extremely stable (being predominantly alkanes) but the penetration is very poor, because they are large stable molecules. Vegetable oils became popular, particularly during the ’70s with the push towards so-called ‘natural’ materials. Note: I have begun calling mineral oil, petrolatum and paraffin wax ‘putrefied wood extracts’ to reflect their true origin.
Still, the vegetable oils, although offering a slight improvement in absorption (probably because they were more compatible with the triglycerides found in the skin lipids), were still quite slow to absorb.
The ’60s and ’70’s saw the expansion of synthetic esters (condensation products made from short chain fatty acids with short chain fatty alcohols, a typical example would be decyl oleate). The widespread use of isopropyl myristate
and isopropyl palmitate in the ’70s was halted recently with the discovery that they implicated in the formation of adult acne (i.e. are comedogenic materials). Still, it must be said that not all synthetic esters are comedogenic, but it can also be said that they offer the cosmetic chemists a vast array of options to affect the percutaneous absorption of cosmetic products. For those who wish to pursue this area I will refer you to an award winning paper by Dr Johann Weichers (of Uniqema Holland) entitled ‘Formulating for Efficacy’ where he outlines a procedure for selection of water phase and oil phase in relationship to drug type, for best efficacy. Other common materials used are cetyl alcohol, stearic acid and glyceryl monostearate that do little for absorption and are only used for their consistency contributing factor. We have also had to endure the change in perception from consumers that have seen oils such a whale oil or mink oil discouraged; fortunately we have found more than adequate replacements with vegetable squalane, jojoba oil and other more exotic emollients. It is known that short chain emollients and straight chain emollients have better absorption characteristics than long chain or branched chain emollients. Emollients that are polyunsaturated also seem to have better penetration characteristics than unsaturated emollients. If they have better penetration characteristics, they also seem to assist with drug delivery.
An interesting oil, finding its way into some formulations, is emu oil. Due to emu oil’s lack of phospholipids it appears to be an excellent oil for skin penetration, and as an anti-inflammatory commonly used in preparations for arthritis.
Intercellular route Transcellular route
Plasma
membrane
Cell
cytoplasm
Fatty acid
Intrinsic protein
Intercellular space
Lipid
Aqueous Figure 2: The intercellular channels. April 2012 PERSONAL CARE 123
Ceramide
Cholesterol/ Cholesterol sulfate
Lipid
Keratin
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