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Permeation Profiles (permeation + profile)
Selected AbstractsAn investigation into the influence of counterion on the RS -propranolol and S -propranolol skin permeabilityJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2010Francesco Cilurzo Abstract The effects of two contra-ions, namely benzoate (Bz) and oleate (Ol), on the in vitro human skin permeability of propranolol racemate (RS -PR) or S -enantiomer (S -PR) were studied. Saline solution (SS) or mineral oil (MO) were selected as vehicles. The MO increased the permeability coefficient (Kp) of PR-Bz (pKp,,,4) of about four times with respect to SS (pKp,,,8) probably due to the ion pair formation. The steady-state flux of S -enantiomers resulted about twofold higher than that of racemates according to their lower melting temperatures with the exception of (S)-PR-Ol and (RS)-PR-Ol vehicled in SS which not resulted statistically different. This anomalous result could be explained considering the behavior of (RS)-PR-Ol or (S)-PR-Ol in aqueous solutions: these salts formed ion pairs which associated to form aggregates up to a concentration of 20,µg/mL as verified by light scattering. Therefore, their effective concentrations in SS resulted similar and justified the overlapped skin permeation profiles. All three considered variables, namely counterion, vehicle, and chirality, resulted mutually interfering on and deeply influenced the passive diffusion process of PR. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1217,1224, 2010 [source] Prediction of steady-state skin permeabilities of polar and nonpolar permeants across excised pig skin based on measurements of transient diffusion: Characterization of hydration effects on the skin porous pathwayJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2002Hua Tang Abstract The applicability of a two-parameter Fickian diffusion model for predicting the skin steady-state permeability based on measurements of the transient transport of permeants across the skin was tested. Using five model permeants possessing different physicochemical properties and pig skin as the model membrane, the skin permeabilities predicted by the two-parameter Fickian diffusion model were compared with the measured skin permeabilities. Results show that the transient skin permeation profiles of the hydrophobic permeants, estradiol, testosterone, and dolichol, across split-thickness pig skin can be modeled adequately by the two-parameter Fickian diffusion model (with constant parameter values), and therefore, that this model can be utilized to shorten the experimental time required to determine the skin permeabilities of these compounds. However, the skin permeabilities of the highly hydrophilic permeants, mannitol and sucrose, predicted by the two-parameter Fickian diffusion model (with constant parameter values) were significantly lower than the experimentally determined values, indicating that the dominant skin pathway of polar permeants within the excised pig skin undergoes significant structural changes during the in vitro diffusion cell studies. Although the skin permeability values determined experimentally using the traditional steady-state method normally correspond to a highly hydrated skin sample, the two-parameter Fickian diffusion model enables an estimation of the skin permeability of the skin membrane at its less-hydrated state (a condition more representative of in vivo and clinical situations). Using the two-parameter Fickian diffusion model and a recently developed skin porous-pathway theory, the effects of skin hydration on the skin porous pathway within the excised pig skin were characterized. Specifically, we found that hydration leads to induction of new pores/reduction of the tortuosity of existing pores within the excised pig skin during the 48 h diffusion cell studies conducted, while the skin average pore radii remain relatively constant (,26 Å) for up to 48 h. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1891,1907, 2002 [source] A bioassay for mosquito repellency against Aedes aegypti: method validation and bioactivities of DEET analoguesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2010Alexander Jahn Abstract Objectives Vector-borne diseases are still a major mortality factor in Africa and South-east Asia and effective mosquito repellents are therefore needed. An efficient and safe in-vitro assay system using artificial blood and skin substitute could facilitate the development of novel repellents, as most assays currently rely on human subjects or vertebrate whole blood. Moreover, examining the skin permeation profiles could provide safer mosquito repellents. The new assay system could serve as an initial system for testing new repellent candidates upon validation with DEET and its analogues. MethodsN,N -Diethyl- meta -toluamide (DEET) and five analogues were synthesised and used to validate a novel in-vitro bioassay using artificial blood and collagen membrane. Repellency against Aedes aegypti was correlated with lipophilicity and skin permeation. Key findings The new in-vitro assay showed good reproducibility (interday relative standard deviation <10% at high concentrations). Four of the five DEET analogues showed repellency similar or superior to that of DEET. Repellency correlated linearly with lipophilicity but stronger repellents tended to permeate skin better. Conclusions The new in-vitro assay using blood substitute and collagen membrane significantly simplifies screening of possible mosquito repellents. Lipophilicity as well as skin permeation profiles should be considered before testing of compounds that are candidates for mosquito repellents. [source] The effects of freezing skin on transdermal drug penetration kineticsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007L. A. AHLSTROM This study investigated the effects of freezing canine skin on the penetration kinetics of hydrocortisone. Skin samples from three dogs were used for in vitro penetration studies commencing on the day of skin collection (fresh skin) and again after freezing at ,20 °C for 1, 4, 8 and 12 months. When the data from the dogs was averaged, the pseudo-steady-state flux (Jss) of hydrocortisone through skin frozen for any duration was significantly (P < 0.023) greater than through fresh skin and there was a positive relationship (P < 0.007) between the length of freezing and ,Jss. For all dogs, the lag times (tlag) calculated for hydrocortisone penetration were significantly (P < 0.029) shorter through skin that had been frozen, compared with fresh skin. However, the shapes of the permeation profiles of hydrocortisone appeared similar through the fresh and frozen dog skins and no differences were detected between the groups on histological examination. The results of this study have shown that freezing dog skin at ,20 °C can significantly increase the transdermal penetration of hydrocortisone in vitro, and that the extent of this enhancement can increase with duration of freezing. [source] | ||||||||||