Influence of membrane-solvent-solute interactions on solute permeation in model membranes.
ABSTRACT The interaction of the components of topical formulations with the skin is an important consideration for effective drug delivery and efficacy. The relative importance of solubility parameters and other solvent properties on membrane diffusion processes has not been fully elucidated in the literature. In this paper, the effect of different vehicles on the permeation of caffeine, salicylic acid and benzoic acid through silicone membranes was evaluated. Polydimethylsiloxane membranes were used as model membranes for comparing the release characteristics of saturated solutions of model permeants because of their homogeneity and uniformity. Log P (octanol-water partition coefficient) and solubility parameter values were calculated for the compounds under study. In vitro diffusion studies indicated that the permeation profiles of all solutes showed a similar pattern. The permeation rates of benzoic acid and salicylic acid through silicone membrane from saturated solutions were higher than those for caffeine reflecting the more lipophilic nature of these compounds in comparison with caffeine. Solvent uptake studies confirmed that the vehicles that were highly sorbed by the membrane altered its properties and hence the flux. Vehicles that were not sorbed by the membrane showed similar steady-state fluxes for the model drugs. This suggests that the diffusion process is mainly influenced by the interactions between the vehicles and the membrane. Solubility parameter alone cannot explain the interactions between the membrane and the vehicles in all cases. Rather, it is likely that membrane flux reflects a combination of different solvent and solute characteristics, such as size, shape and charge distribution.
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ABSTRACT: Abstract Context: The membrane-coated fiber (MCF) array technique was previously demonstrated to be a rapid, quantitative assessment of the percutaneous absorption of volatile compounds, capable of studying chemical mixtures and their synergistic effects. In particular, three commercially available fiber coatings (polydimethylsiloxane, polyacrylate and carbowax) were shown to be representative of molecular interactions relevant to skin absorption. Objective: This study evaluated the potential use of these fibers as a high throughput screening approach for topical formulations. More specifically, the MCFs were evaluated for their ability to predict the skin permeability of caffeine (CF), cortisone (CT), mannitol (MN) and salicylic acid (SA) applied in water or ethanol as unsaturated and/or saturated concentrations, using an additional extraction step to obtain analytes appropriate for liquid chromatography. Methods: Compound extraction from a donor solution was carried out by fiber immersion for a set period of time. The compound was then re-extracted into acetonitrile and quantitated by liquid chromatography coupled to a mass spectrometer. Radiolabel equivalents of the compounds were analyzed in a similar manner with the exception of detection method used. Results: Fiber extraction of radiolabeled compounds (CF, MN, SA in water) was proved to be unsuccessful, whereas the extraction of their non-radiolabeled equivalents (CF, CT, SA) revealed poor linearity, and poor between-day and within-day reproducibility. Similar unsatisfactory results were observed regardless of whether a single fiber was used, or whether multiple fibers were used simultaneously. Furthermore, incompatibility between the MCF and solvent (vehicle) was observed, which disputes its potential use as a formulation screening technique. Conclusion: On the basis of these findings, the MCF array is not suitable to describe the vehicle effects on skin absorption of non-volatile compounds.Cutaneous and Ocular Toxicology 04/2013; · 1.04 Impact Factor
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ABSTRACT: Drug loaded hydrofluoroalkane (HFA) sprays can generate effective pharmaceutical formulations, but a deeper understanding of the manner in which these dynamic systems drive the process of in situ semi-solid dosage form assembly is required. The aim of this study was to investigate the effect of the matrix assembly and composition on drug localisation in human skin. Comparing the characteristics of sprays constituting HFA 134a, ethanol (EtOH), poly(vinyl pyrrolidone) K90, isopropyl myristate (IPM), and poly(ethylene glycol) (PEG) demonstrated that the addition of non-volatile solvents acted to delay EtOH evaporation, control the degree of drug saturation (DS) and enhance the corticosteroid delivery from HFA spray formulations. In a dose matched skin penetration study the HFA sprays containing only EtOH as a co-solvent delivered 2.1μg BMV (DS 13.5) into the tissue, adding IPM to the EtOH HFA delivered 4.03μg BMV (DS 11.2), whist adding PEG to the EtOH HFA delivered 6.1μg BMV (DS 0.3). Compared to commercial cream (delivering 0.91μg BMV) the EtOH/PEG HFA spray deposited over 6 times (p<0.05) more drug into the skin. Post spray deposition characterisation of the semi-solid suggested that the superior performance of the EtOH/PEG HFA spray was a consequence of retarding EtOH evaporation and presenting the drug in an EtOH rich PEG residual phase, which promoted BMV passage through the SC and into epidermis.International Journal of Pharmaceutics 05/2013; · 3.99 Impact Factor
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ABSTRACT: In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo. Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS). The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity. The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.Pharmaceutical Research 08/2013; · 4.74 Impact Factor