Other Solvents

Several other solvents are used extensively in topical formulations. Isopropyl myristate (IPM) could be classified as an oily ingredient, which can be grouped within a series of isopropyl fatty acid esters such as isopropyl linoleate and iso-propyl palmitate. IPM has been included in emulsions and gels at around 10%

and at 2% in lotions. It penetrates readily into the skin, and can affect partitioning and permeation of other compounds into and through the membrane. For example, Brinkmann and Muller-Goymann (2005) showed that IPM integrated into the lipophilic regions of the stratum corneum lipid matrix, an effect that was enhanced when IPM was used as a co-solvent with propylene glycol. IPM is generally accepted to be non- or only very mildly sensitising to the skin and so is a useful solvent for topical dosage forms (Uter et al., 2004).

Oleic acid is also used in some topical formulations such as White Liniment BP. However, oleic acid has been shown to effectively enhance delivery of numerous chemicals to and through human skin, and indeed is widely regarded as one of the most potent penetration enhancers. For example, oleic acid increased the flux of salicylic acid 28-fold and 5-flourouracil flux 56-fold through human skin membranes in vitro (Goodman and Barry, 1989). The fatty acid is effective at relatively low concentrations (typically less than 10%) and can work synergistically when included in formulations with other solvents such as propy-lene glycol or dimethyl isosorbide. Considerable efforts have been directed at investigating the interactions of oleic acid with human skin constituents. It is clear from numerous literature reports that oleic acid interacts with and modifies the lipid domains of the stratum corneum, as would be expected for a long chain fatty acid with a cis-configuration. Spectroscopic investigations using deuterated oleic acid in human stratum corneum indicates that oleic acid at higher concentration can also exist as a separate phase (or as 'pools') within the bilayer lipids (Ongpipattanakul et al., 1991). More recently, electron microscopic studies have shown that a discreet lipid domain is induced within stratum corneum bilayer lipids on exposure to oleic acid (Tanojo et al., 1997). The formation of such pools would provide permeability defects within the bi-layer lipids thus facilitating permeation of hydrophilic permeants through the membrane and increasing partitioning of lipophilic drugs into the oleic acid phase.

Silicones are polymers comprising alternate atoms of silicon and oxygen, with organic groups attached to the silicon atoms. Various grades are available and so they have many uses as resins, waxes and rubbers, including use as ad-hesives for topical application. Dimethicones (Dimeticone in Europe) are fluid silicones with the organic element a methyl group. These fluid silicones are water repellent and have been used to protect the skin from water soluble irritants. Thus they have been used to protect against bed sores and diaper rash. However, though rare, adverse reactions to silicones have been reported, notably when used for joint or breast implants.

Many other excipients are incorporated into topical preparations, including preservatives, fragrance materials and surfactants. Though not typically employed as solvents per se, these materials may have solubilising properties, such as sodium lauryl sulphate or terpene fragrances. Again, many of these materials can interact with the stratum corneum to modify drug delivery.

0 0

Post a comment