Penetration enhancement propylene glycol

As recently reviewed by Gupta and Garge (2002), there are some materials known to penetrate the skin readily and appear to be capable of acting as penetration enhancers for certain selected drugs. These enhancers sometimes work more effectively in the presence of solvents such as ethanol or propylene glycol. A well-known example is the use of the insect repelent DEET (N,N diethyl-m-toluamide) as an enhancer for corticosteroids or the use of isopropyl myristate and propylene glycol for diclofenac sodium. Indeed, cyclodextrins have also been employed as penetration enhancers for hydrocortisone although how this system functions is not easy to visualize (see later section on cyclodextrins). 

Barry B, Williams A. Human skin penetration enhancement the synergy of propylene glycol with terpenes. Proc Int Symp Control Release Bioactive Mater 1989 16 33-34. 

Williams, A.C., and B.W. Barry. 1989. Urea analogues in propylene glycol as penetration enhancers in human skin. Int J Pharm 56 43. 

Vaddi, H.K., P.C. Ho, and S.Y. Chan. 2002. Terpenes in propylene glycol as skin-penetration enhancers Permeation and partition of haloperidol, Fourier transform infrared spectroscopy, and differential scanning calorimetry. J Pharm Sci 91 1639. 

Vaddi, H.K., et al. 2003. Oxide terpenes as human skin penetration enhancers of haloperidol from ethanol and propylene glycol and their modes of action on stratum corneum. Biol Pharm Bull 26 220. 

Transdermal delivery is a case in point. The skin, particularly the stratum corneum presents a formidable barrier to diffusion. Materials used to enhance its permeability have ranged from simple solvents such as ethanol or propylene glycol to aromatic chemicals such as terpenoids. Such penetration enhancers appear to work by disrupting the lipid domains in the stratum... 

The authors of the last report suggested that the whole structure of minoxidil is required for sensitization and that propylene glycol in the formulation of minoxidil that is used therapeutically increases the penetration of minoxidil into the skin, enhancing the risk of a reaction. 

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. 

Formulations containing an absorption promoting substance, such as propylene glycol or sodium lauryl sulphate, may increase the permeability of the stratum comeum to water-soluble drugs. Propylene glycol is a commonly used vehicle in topical corticosteroid preparations for veterinary use. Various aprotic solvents, which include dimethylacetamide, dimethylformamide, dimethylsulphoxide, tetrahydrofurfuryl alcohol, and 2-pyrrolidone, serve as penetration enhancers of polar drugs (Barry, 1983). Dimethylsulphoxide... 

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 ... 

Williams AC and Barry BW. Urea Analogues in Propylene Glycol as Penetration Enhancers in Human Skin. IntJPharm 1989 56 43-50. 

On the other hand, SEPA (2-n-nonyl-l,3-dioxolane) has been shown to be a more versatile penetration enhancer in terms of its ease of formulation, chemical stability and its ability to enhance the skin penetration of a wide variety of compounds of varying physicochemical characteristics. Permeants that have been evaluated include indomethacin, ibuprofen, minoxidil, acyclovir, caffeine, econazole, papaverine, progesterone and estradiol. The degree of skin penetration enhancement using SEPA is dependent on the physicochemical characteristics of the permeant. For example, following application of indomethacin in a simple ethanol-propylene glycol vehicle to human skin in vitro, cumulative absorption over 24 h amounted to 0.7 percent of the applied dose. The addition of 2 percent SEPA to the vehicle increased the 24 h absorption value to 23 percent of the applied dose (Marty et al. 1989). Furthermore, in comparative studies between SEPA and Azone, SEPA was shown to be a more effective human skin permeation enhancer for indomethacin (Figure 14.6, Marty et al. 1989). 

Priborsky, J., Takayama, K., Nagai, T., Waitzova, D., and Elis, J. (1987). Combination effect of penetration enhancers and propylene glycol on in vitro transdermal absorption of insulin. Drug. Des. Deliv., 2 91-97. 

Yamane, M.A., Williams, A.C., and Barry, B.W. (1995). Terpene penetration enhancers in propylene glycol/water co-solvent systems effectiveness and mechanism of action, J. Pharm. Pharmacol, 47 978-989. 

Perfusion of skin with transdermal-penetration-enhancing agents such as ethanol, DMSO-ds and propylene glycol was studied by in vitro P NMR [39]. Epidermal strips from abdominal pig skin were placed in a 10 mm O.D. NMR tube modified for continuous perfusion with buffered salt solution and a serial spectra were recorded on a Broker AMX500 spectrometer. Signal intensities for phosphomono- and di-esters PME and PDE, phosphocreatine PCr, inorganic phosphate Pi and nucleotide triphosphorate, >3-NTP were followed in time. Additional spectra were recorded when the perfusion medium contained dexamethasone. The dexamethasone perfusion resulted in a dose-dependent decrease in PCr and NTP levels and had an effect on PME metabolism. 

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]. 

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