Comparison of the percutaneous absorption of hydrophilic and lipophilic compounds in shed snake skin and human skin.

The in vitro transdermal permeation of eight hydrophilic drugs (antipyrine, L-dopa, dopamine hydrochloride, diclofenac sodium, 5-fluorouracil, isoprenaline hydrochloride, nicorandil and morphine hydrochloride) and eight lipophilic drugs (aminopyrine, cyclobarbital, ibuprofen, indomethacin, isosorbide dinitrate, flurbiprofen, ketoprofen and lignocaine) was determined using shed snake skin of Elaphae obsoleta and human skin. The permeation parameters and physiological characteristics of the skin, e.g. the water and lipid content, and the thickness of shed snake skin and human skin were evaluated and compared. In shed snake skin, the permeability coefficients (P) of lipophilic drugs were in the same range as those through the human skin (0.9 to 1.8-times); whereas those of hydrophilic drugs were remarkably lower (3.3 to 6.1-times). The thickness and lipid content of shed snake skin and human stratum corneum were not significantly different (P > 0.05), whereas the water content of shed snake skin was significantly lower than that of human stratum corneum (P < 0.05). The lower permeability of shed snake skin for hydrophilic compounds might be caused by the lower porosity of skin strata. The results suggested a potential use of shed snake skin as barrier membrane for lipophilic compounds percutaneous absorption studies in vitro.

Effect of chitosan salts and molecular weight on a nanoparticulate carrier for therapeutic protein.

The objective of this study was to investigate the potential of chitosan salts as a carrier in the preparation of protein-loaded nanoparticles. Glutamic and aspartic acids were used to prepare chitosan salts of 35, 100, and 800 KDa. Nanoparticles of chitosan base, chitosan glutamate, and chitosan aspartate were produced by ionotropic gelation with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model protein at loading concentrations ranging from 0.2 to 2 mg/mL. The size of the nanoparticles, as measured by photon correlation spectroscopy, was in the range of 195 to 3450 nm, depending on type and molecular weight of chitosan. Nanoparticles prepared with higher molecular weight chitosan showed larger sizes. The encapsulation was controlled by the competition of BSA in forming ionic cross-linking with chitosan and by the entrapment of BSA during the gelation process. Higher BSA encapsulation efficiency (EE) was obtained for nanoparticles prepared with chitosan salts compared to those prepared with the base. The higher EE was a result of a higher degree of ionization, causing more active sites to interact with BSA. In addition, a higher and faster release of BSA from the nanoparticles into pH 7.4 buffer medium was observed for nanoparticles of the chitosan salts than was observed for nanoparticles of the chitosan base. The higher and faster release was attributed to higher EE and lower entrapment of BSA within the matrix of the nanoparticle during the gelation process. The influence of molecular weight on the property of nanoparticles exhibited different effects. The difference was a result of different organic acids used to prepare nanoparticles leading to the difference in polymer conformation and viscosity of organic acid solution. Therefore, this study showed that the characteristics of chitosan nanoparticles loaded with a protein drug could be readily modulated by changing the salt form or the molecular weight of the chitosan carrier.

Dual ambroxal and chlorpheniramine resinate as an alternative carrier in concurrent resinate administration.

Two classical resinates, ambroxal (AMX) resinate and chlorpheniramine (CPM) resinate, and a novel formulation of dual AMX and CPM resinate were prepared by the batch method. The dissolution behavior of the drug from the classical resinates, a mixture of two classical resinates, and the dual-drug resinate in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was examined and compared. The equilibrium of drug on to the resin and the re-exchange of the drug on to the resinate were also investigated. The drug release pattern from the resinate followed the particle diffusion process. The type of dissolution medium affected the amount of drug released from the resinate. The amount of drug released from the dual AMX and CPM resinate was not significantly different from that from the classical AMX resinate or CPM resinate (p < 0.05), but was considerably higher than that from the concurrent administration of two classical resinates (p > 0.05). These results indicated that the concurrent administration of the resinates affected drug release from the resinate, and the dual-drug resinate can be used as an alternative carrier for an ion-exchange delivery system.

Age difference in simultaneous permeation and metabolism of ethyl nicotinate in rat skin.

The age-dependent characteristics of transdermal permeation of ethyl nicotinate (EN) and its metabolism to nicotinic acid (NA) were examined in rats at the ages of a fetus at 21 d, 3, 10, 50, 270 and 360 d. Skin transport in vitro was investigated using mounted skin in side-by-side diffusion chambers, and flux of EN and NA was determined. With developing and aging in rats, EN flux from EN-saturated solution declined gradually, however, NA flux increased drastically at 10 and 50 d. To elucidate the mechanism of this age-dependent escalation of NA flux, a hydrolysis study was performed using skin homogenate, and the Michaelis-Menten parameters (Vmax and Km) of EN were evaluated. Vmax and Vmax/Km ratio showed the same tendency with NA flux/total (EN+NA) flux ratio, suggesting that skin esterases in rats are developed gradually after birth, then increase markedly and become steady in the adult period. On the other hand, the affinity parameter, Km, was almost the same among all ages. Moreover, metabolic saturation of esterase during the transdermal process occurred in all ages, and maximal NA flux and EN concentration in the donor compartment for the maximal NA flux were also affected by age. These findings indicated that the discrepancy in transdermal profiles of EN among the ages tested was dominantly due to the difference in the development of esterase in the growth process.

Age-related changes in skin permeability of hydrophilic and lipophilic compounds in rats.

The effect of age on intact and stripped skin permeability of lipophilic (ketoprofen and isosorbide dinitrate) and hydrophilic permeants (deuterium oxide and diclofenac sodium) was investigated using STD: Wistar male rats aged 5 to 180 days. The permeability of permeants through intact skin increased with increasing lipophilicity of the permeants at each age, indicating that the permselective property of rat skin is revealed even at 5-days-old. The permeability coefficients through intact skin decreased with increasing age, and the extent of these decreases was higher for lipophilic permeants than that for hydrophilic permeants. On the other hand, the stripped skin permeability of permeants was almost the same at each age, and with aging each permeability coefficient through stripped skin decreased up to 21 days, dramatically during 21-90 days and then gradually again to 180 days. The thickness of the stratum corneum and stripped skin increased according to age with faster growth during 21-90 days. The reciprocal of the mean thickness of stratum corneum and stripped skin correlated well with intact skin and stripped skin permeability (r > 0.9), respectively. These results clarified that the permselectivity of rat skin against lipophilicity of permeant exists at the latest from 5 days after birth. In addition, it is speculated that the thickness of skin is a large factor in the decrease of its permeability with age.