Hairless mouse skin and

The purpose of this report is to present results on (a) the effect of ethanol on the transport of 8-estradiol across hairless mouse skin and (b) the effect upon the effective permeability coefficient as solvent compositions are independently varied in the donor and receiver chambers. Also, since there is evidence for pore formation, at least at the highest ethanol levels, a novel pore model... 

In 1994, Menon and co-workers [74] similarly used TEM to visualize tracers in the stratum comeum after sonophoresis treatment. They applied colloidal lanthanum and fluorescein-conjugated dextran (MW 40,000) to hairless mouse skin and treated the site with 15 MHz (0.1 W/cm ) for 5 minutes. As before, the tracers were observed in intercellular lacunae at different levels of the stratum comeum (see Fig. 9). Electron microscopy of horizontal sections further revealed that the tracers were found within interconnected lacunae. It was suggested that sonophoresis may cause lipid-phase separation, thereby forming continuous chaimels that divide the lipid bilayers and amplify an intercellular transport pathway. 

If either of these last two explanations is the source of the reduced flux from a saturated soil or pure powder compared with saturated water, then the larger lag time calculated for subjects E and F (i.e., 1.56 and 1.04 h, respectively) would represent diffusion through the SC. As a result, flux through the SC should be calculated using these values of rather than 0.58 h estimated for CP absorption from saturated water. When calculated this way, is approximately 7 pg cm" h , which is about 1/lOth of determined from saturated water. This is similar to the in vitro results summarized in Table 11.3 for pure powder and saturated water. These data are also consistent results observed in vitro with hairless mouse skin and for cellulosic membranes (Touraille etal., 1998, 2005) The steady-state fluxes of CP measured from saturated soil and pure powders are approximately an order of magnitude smaller than those from an aqueous saturated solution. 

Fig. 4 Generalized permeation profile. From left to right the data are for n-butanol permeating hairless mouse skin at 20°, 25°, and 30° C respectively. Increasing temperature raises the flux (slope) and shortens the lag time. 

H. Durrheim, G. L. Flynn, W. I. Higuchi, and C. R. Behl. Permeation of hairless mouse skin. I Experimental methods and comparison with human epidermal permeation by alkanols. J. Pharm. Sci. 69 781-786 (1980). 

J.-C. Tsai, M. J. Cappel, N. D. Weiner, G. L. Flynn, and J. Ferry. Solvent effects on the harvesting of stratum corneum from hairless mouse skin through adhesive tape stripping in vitro. Int. J. Pharm. 68 127-133 (1991). 

N-Mannich derivatization has also been documented to improve skin delivery [91][92], In the case of theophylline (11.56) and 5-fluorouracil (11.58), a much improved solubility in water of the various N-Mannich bases examined was observed. To avoid breakdown, however, the prodrugs had to be dissolved in a polar nonaqueous solvent (isopropyl myristate) for pharmaceutical use. The delivery of theophylline and 5-fluorouracil through hairless mouse skin was, thus, accelerated approximately sixfold through use of the prodrugs 11.57 and 11.59, respectively. 

Walters and Olejnik s ( H) data on methyl nicotinate transfer through hairless mouse skin. All indicate maximal activity residing with the C22 ether. Not only do the latter two studies indicate a falling off in effectiveness as the chain length is increased to and Cia but they also indicate that the oleyl (unsaturated chain) ethers are more active than their saturated analogues. 

In the light of these observations and the newer trends in product formulation, it was decided to study the in vitro release and permeation of propranolol hydrochloride from various hydrophilic polymeric matrices using the cellulose membrane and the hairless mouse skin as the diffusion barriers and to evaluate the effects of some of the additive ingredients known to enhance drug release from dermatological bases. 

The in vitro diffusion studies for each sample were carried out by using the Franz diffusion cells with a diffusional area of about 1.76cm2. The acceptor compartment of the apparatus was filled with the buffer solution pH 6, USP [21], and maintained at 37 0.5°C via a circulating water system. The diffusion membrane (the cellulose membrane with a molecular weight cut-off point of 1000 or the hairless mouse skin) previously prepared was placed between die donor and the acceptor compartments of the assembly. An accurately weighed 4g of sample was then placed in the donor cell and the diffusion process was started. The solution in the acceptor compartment was continuously stirred with a small magnetic stirrer to maintain the sink conditions. Aliquots from the receptor cells were removed at 0.5,2,4, 8 and 24 h time intervals and replaced with equal... 

Monti D, Giannelli R, Chetoni P, Burgalassi S. Comparison of the effect of ultrasound and of chemical enhancers on transdermal permeation of caffeine and morphine through hairless mouse skin in vitro. Int J Pharm 2001 229 131-137. 

Terpenes continue to be a popular choice as experimental enhancers for delivering materials across skin membranes. For example, L-menthol facilitated in vitro permeation of morphine hydrochloride through hairless rat skin [37], imipramine hydrochloride across rat skin [59], and hydrocortisone through hairless mouse skin [60]. Recently, niaouli oil was found to be the most effective of six essential oils in promoting estradiol penetration through hairless mouse skin [61]. It is noteworthy that there is currently little control on the topical use of most terpenes, and many aromatherapy oils and formulations contain appreciable quantities of these chemicals. Their excessive use offers potential for permeation of hazardous compounds from the same formulations into the skin some terpenes also have pharmacological activity. 

Many studies have employed phospholipids as liposomes (vesicles) to transport drugs into and through human skin. However, a few investigations have also employed phospholipids in a nonvesicular form as penetration enhancers. For example, 1% phosphatidylcholine in PG, a concentration at which liposomes would not form, enhanced theophylline penetration through hairless mouse skin [64]. Similarly, indomethacin flux was enhanced through rat skin by the same phospholipid and hydrogenated soybean phospholipids increased diclofenac permeation through rat skin in vivo. 

Bond, J.R., and B.W. Barry. 1986. Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin Hydration damage. J Invest Dermatol 90 486. 

Sarpotdar, P.P., and J.L. Zatz. 1986. Evaluation of penetration enhancement of lidocaine by non-ionic surfactants through hairless mouse skin in vitro. J Pharm Sci 75 176. 

Van den Bergh, B.A., et al. 1999. Elasticity of vesicles affects hairless mouse skin structure and permeability. J Control Release 62 367. 

Pikal, M.J., and S. Shah. 1990. Transport mechanisms in iontophoresis. II. Electroosmotic flow and transference number measurement for hairless mouse skin. Pharm Res 1 (3) 213. 

Bath, D.B., et al. 2000. Scanning electrochemical microscopy of iontophoretic transport in hairless mouse skin. Analysis of the relative contribution of diffusion, migration, and electroosmosis to transport in hair follicles. J Pharm Sci 89 1537. 

Liu, R, Higuchi, W., Ghanem, A., Bergstrom, T., and Good, W. Assessing the influence of ethanol on simultaneous diffusion and metabolism of P-estradiol in hairless mouse skin for the asymmetric situation in vitro. Int. J. Pharm. 78 123-136, 1992. 

S. M. Dowton, Z., Hu, C. Ramachandran, D. F. H. Wallach, and N. Weiner, Influence of liposomal composition on topical delivery of encapsulated cyclosporin A, I. An in vitro study using hairless mouse skin, STP Pharma Sciences 3 404-407 (1993). 

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