Penetration enhancement oleic acid

Many other papers have described the use of DSC in the predication of penetration eidiancement using the following penetration enhancers oleic acid/propylene glycol [20], straight chain fatty acids, monosaturated and polyunsaturated fatty acids [21], carvone [22], menthol [23], 5-aminolevulinic acid [24], and phospholipids [25]. 

Other fatty acids as absorption enhancers have been reported. Ogiso et al. [112] demonstrated that lauric acid (C12) produced the largest increase in permeation rate, penetration coefficient, and partition coefficient of propranolol. Onuki et al. [113] reported that docosa-hexaenoic acid (DHA) has a strong insulin permeability enhancement effect and little toxicity, compared to oleic acid and eicosapentaenoic acid (EPA) using a water-in-oil-in-water (W/O/W) multiple emulsion with no or little mucosal damage. 

Penetration enhancers have different mechanisms of action depending on their physicochemical properties. Some examples of penetration enhancers and their mechanisms are bile salts (micellization and solubilization of epithelial lipids), fatty acids such as oleic acid (perturbation of intracellular lipids) [25,26], azone (l-dodecylazacycloheptan-2-one) (increasing fluidity of intercellular lipids), and surfactants such as sodium lauryl sulfate (expansion of intracellular spaces). The complete list of enhancers and their mechanism of actions are discussed in detail in Chapter 10. 

A wide variety of long-chain fatty acids increase transdermal delivery the most popular is oleic acid. It is relevant that many penetration enhancers contain saturated or unsaturated hydrocarbon chains and some structure-activity relationships have been drawn from the extensive studies of Aungst et al. [22,23] who employed a range of fatty acids and alcohols, sulfoxides, surfactants, and amides as enhancers for naloxone. From these experiments, it appears that saturated alkyl chain lengths of around Cio to C12 attached to a polar head... 

The most extensively studied amphiphilic and lipophilic penetration enhancers are oleic acid, oleyl surfactants, terpenes, alcohols, azone, azone analogues [84— 86], and FFAs. 

Figure 16 CH2 asymmetric stretching frequencies, VajCH2 (originating from the SC lipids), as a function of SC weight removed, following treatment with ethanol alone (O) or 5% (v/v) [ H] oleic acid in ethanol ( ). Mean SD, n = 7 or 8. (From Ref. 153. Reprinted from Journal of Controlled Release, 37, Naik et al. Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans, pp. 299-306,1995, with kind permission from Elsevier Science, NL, Sara Burgerhartstraat 25, 1055 KV, Amsterdam, The Netherlands.)...

Yamane, M. A., Williams, A. C. and Barry, B. W. Effects of terpenes and oleic acid as skin penetration enhancers towards 5-fluorouracil as assessed with time permeation, partitioning and differential scanning calorimetry. International Journal of Pharmaceutics 776 237-251, 1995. 

Naik, A. et al. Mechanism of oleic-acid induced skin penetration enhancement in vivo in humans. Journal of Controlled Release 57 299-306, 1995. 

Topical applications in the form of spray also have been reported as vehicles for enhanced frawi-dermal delivery of drugs such as testosterone, estradiol, progesterone, and norethindrone acetate. More effective drug penetration was reported with enhancers padimate and octyl salicylate and compared with laurocapram and oleic acid (38). Other methods reported for enhanced percutaneous drug absorption include iontophoresis (39), ultrasound or sonophoresis (40), and electroporation (41). 

Surfactants—traditionally common constituents and stabilizers of topical vehicles, ranging from hydro-phobic agents such as oleic acid to hydrophilic sodium lauryl sulphate— have been tested as penetration enhancers to improve transdermal drug delivery. 

Patel, D.C. Chang, Y. Penetration Enhancement with Binary System of Oleic Acid, Oleins, and Oleyl Alcohol with Lower Alcohols. US Patent 4,863,970, September 5, 1989. 

Murakami T, Yoshioka M, Yumoto R. Topical delivery of keloid therapeutic drug, tranilast, by combined use of oleic acid and propylene glycol as a penetration enhancer evaluation by skin microdialysis in rats. J Pharm Pharmacol 1998 50 49—54. 

Most drugs do not penetrate epithelial barriers at rates sufficient for clinical usefulness without permeability enhancers, chemicals that are routinely added to dermal drug delivery products. 18 For example, using human skin in an in vitro study, it was demonstrated that sodium dichlofenac (K = 0.70) permeability was enhanced by a mixture containing the lipophiles oleic acid (K = 7.64) and c/-limonene (K = 4.57)J191... 

Movement of penetrants across the mucous membranes is by diffusion. At steady state, the amount of a substance crossing the tissue per unit of time is constant and the permeability coefficients are not influenced by the concentration of the solutions or the direction of nonelectrolyte transfer. As in the epidermis of the skin, the pathways of permeation through the epithelial barriers are intercellular rather than intracellular. The permeability can be enhanced by the use surfactants such as sodium lauryl sulfate (a cationic surfactant). An unsaturated fatty acid, oleic acid, in a propylene glycol vehicle can act as a penetration enhancer for diffusion of propranolol through the porcine buccal mucosa in vitro. Delivery of biopharmaceuticals across mucosal surfaces may offer several advantages over injection techniqnes, which include the following ... 

Oleic acid Has been used as a component of arachis oil Potent penetration enhancer... 

The combined effect of (3-CyD with absorption enhancers such as sodium glycocholate or Azone on the nasal absorption of human fibroblast interferon- 3 in powder form in rabbits has been described. HP- 3-CyD was useful as a biocompatible solubilizer for lipophilic absorption enhancers involved in the nasal preparations of peptides.When insuUn was admiifistered nasally to rats, simultaneous use of an oily penetration enhancer, HPE-101, (l-[2-(decylthio)-ethyl]azacyclopentane-2-one) or oleic acid solubilized in HP-(3-CyD showed a marked increase in serum immuno-reactive insulin levels and marked hypoglycemic (Figure 40.11). The potentiation of the enhancing effect of HPE-101 by HP-(3-CyD can be explained by the facilitated transfer of HPE-101 into the nasal mucosa. Studies on the release of membrane proteins and scanifing electron microscopic observations of rat nasal mucosa indicated that the local mucosal damage due to the combination with HP- 3-CyD may not be serious obstacles to their safe use. 

Jiang, S.J. and Zhou, X.J. (2003). Examination of the mechanism of oleic acid-induced percutaneous penetration enhancement an ultrastructural study, Biol Pharm. Bull, 26 66-68. 

The cubic and hexagonal phases based on GMO/water and GMO/oleic acid/ water, respectively, are well studied and were shown to have the ability to sustain the release of incorporated compounds [59, 67, 68]. Moreover, each component constructing either the cubic or the hexagonal phase is a penetration enhancer by itself. GMO is known to promote ceramide extraction and enhancement of lipid fluidity in the stratum corneum, and oleic acid is considered to increase epidermal permeability via a mechanism involving perturbation of the stratum corneum lipid bilayers and lacunae formation [69]. 

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