Article

Assessment of drug permeability distributions in two different model skins.

Department of Pharmaceutics, Faculty of Pharmacy, Gomal University, Dera Ismail Khan (NWFP), Pakistan.
International Journal of Pharmaceutics (Impact Factor: 3.99). 11/2005; 303(1-2):81-7. DOI: 10.1016/j.ijpharm.2005.07.005
Source: PubMed

ABSTRACT Past in vitro studies with human skin have indicated that drug permeability coefficient (Kp) distributions do not always follow a Gaussian-normal pattern. This has major statistical implications, exemplified by the fact that use of t-tests to evaluate significance is limited to normally distributed populations. Percutaneous absorption research often involves using animal or synthetic skins to simulate less readily available human skin. However, negligible work has been performed on assessing the permeability variabilities of these model membranes. This paper aims to fill this gap. To this end, four studies were undertaken representing two different drugs (caffeine and testosterone) with each drug penetrating through two different model skins (silicone membrane and pig skin). It was determined that in the silicone membrane studies, both compounds' Kp distributions could be fitted to a normal pattern. In contrast, in the pig skin studies, there were notable differences between each drug. While the testosterone Kp values could be fitted to a normal distribution, this was not possible with the caffeine Kp data, which could be fitted to a log-normal distribution. There is some evidence from the literature as well as physicochemical considerations that these outcomes may reflect general trends that are dependent upon both membrane and penetrant properties.

1 Bookmark
 · 
136 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of cutaneous leishmaniasis (CL) is a dream for the patients, health care authorities and scientists. The aim of this study was to develop a topical liposomal meglumine antimoniate (MA, Glucantime(TM)) (Lip-MA) formulation and evaluate the therapeutic effects of the preparation on lesion induced by L. major in BALB/c mice. Liposomes containing 22.5% MA (6.4% Sb(+5)) with and without oleic acid (LMA-OA and LMA) were formulated using fusion method plus homogenization and characterized for the size and encapsulation efficiency. The penetration of MA from the LMA-OA and LMA formulations through and into the skin was checked in vitro using Franz diffusion cells fitted with mouse skin at 37 ˚C for 8 h. The in vitro permeation data showed that almost 1.5% of formulations applied in the mouse skin were penetrated and the amount retained in the skin was about 65%. The 50% effective dose of LMA and LMA-OA against amastigotes of L.major was 46.36 and 41.01 μg/ml, respectively. LMA or LMA-OA was used topically twice a day for 4 weeks to treat the lesion induced by L. major in susceptible BALB/c mice. The results showed a significantly (P < 0.001) smaller lesion size in the treated groups of mice compared to the control groups which received either empty liposomes or phosphate-buffered saline (PBS). The spleen parasite burden was significantly (p < 0.001) lower in the treated groups compared to the control groups receiving either empty liposomes or PBS at the end of the treatment period. However, when the treatment was stopped, the lesion size progressed and spleen parasite burden increased in LMA and LMA-OA groups, but still was significantly less than the control groups (p<0.05). There was no significant difference between the two formulations of LMA and LMA-OA. The results suggested that topical liposomes containing MA might be an appropriate choice for clinical trials for the treatment of CL.
    Experimental Parasitology 04/2014; · 2.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study evaluates the potential application of micellar liquid chromatography (MLC) to predict skin permeation with a series of model compounds. MLC has previously been found to be useful in the prediction of partition coefficient values (logP) for pharmaceutical compounds, yet has not been incorporated in skin permeability models prior to this work. This article provides statistically supported data that this technique enhances the ability to predict the permeability of similar drugs through the skin (Kp). The replacement of a traditional physicochemical parameter, namely the octanol-water partition coefficient (logPow) with a chromatographically determined value (logPmw), results in a quantitative partition-permeability relationship that is robust to variation. MLC offers many benefits compared with the traditional techniques employed to obtain logP values.
    European Journal of Pharmaceutical Sciences 08/2013; · 2.99 Impact Factor
  • Source

Full-text

Download
165 Downloads
Available from
Jun 4, 2014