Investigation of the permeation of model formulations and a commercial ibuprofen formulation in Carbosil® and human skin using ATR-FTIR and multivariate spectral analysis

The purpose of the present study was to use attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and target factor analysis (TFA) to investigate the permeation of model drugs and formulation components through Carbosil® membrane and human skin. Diffusion studies of saturated solutions in 50:50 water/ethanol of methyl paraben (MP), ibuprofen (IBU) and caffeine (CF) were performed on Carbosil® membrane. The spectroscopic data were analysed by target factor analysis, and evolution profiles of the signal for each component (i.e. the drug, water, ethanol and membrane) over time were obtained. Results showed that the data were successfully deconvoluted as correlations between factors from the data and reference spectra of the components, were above 0.8 in all cases. Good reproducibility over three runs for the evolution profiles was obtained. From the evolution profiles it was observed that water diffused better through the Carbosil® membrane than ethanol, confirming the hydrophilic properties of the Carbosil® membrane used. IBU diffused slower compared with MP and CF. The evolution profile of CF was very similar to that of water, probably because of the high solubility of CF in water, indicating that both compounds are diffusing concurrently. The second part of the work involved a study of the evolution profiles of the components of a commercial topical gel containing 5% (w/w) of ibuprofen as it permeated through human skin. Although the system was much more complex, data were still successfully deconvoluted and the different components of the formulation identified except for benzyl alcohol which might be attributed to the low concentrations of benzyl alcohol used in topical formulations. (C) 2009 Elsevier B.V. All rights reserved.

Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

In addition to its hyperphagic effect in rats, 8-OH-DPAT also reduces grooming, but it is uncertain whether the inhibition of grooming is a specific effect or a consequence of response competition from eating. The present experiments explored the effects of 8-OH-DPAT on periprandial grooming and grooming elicited by spraying rats with water. Momentary time sampling over 30 or 60 min, with behaviour scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face grooming, body grooming, genital grooming and resting) at 15s intervals, was used for data collection. Non-deprived rats were tested in the presence and absence of food and baseline grooming levels were manipulated by spraying the dorsal surface of the back with water. Data were submitted to ANOVA. The first experiment confirmed that 8-OH-DPAT increased food intake and that this was associated with a parallel increase in feeding observations; active observations were also increased, but resting and total grooming observations were reduced: scratching was reduced even at 0.003mg/kg, face- and body-grooming were reduced at doses > 0.03mg/kg and genital-grooming was least sensitive, only being reduced at 0.1mg/kg. The second experiment revealed that spraying with water had no effect on food intake, feeding or resting observations, but increased total grooming (largely due to increased body-grooming) and reduced activity observations. In rats sprayed with water, 8-OH-DPAT increased food intake (0.1mg/kg) and observations of feeding (0.003 & 0.1mg/kg), but total grooming was dose-dependently inhibited, with genital-grooming most sensitive(> 0.003mg/kg), followed by face-grooming (> 0.01mg/kg) and body-grooming (>0.03mg/kg), whilst low levels of scratching were unaffected. The final experiment tested water-sprayed rats in the absence of food: 8-OH-DPAT increased resting and reduced total grooming, mostly as a consequence of reductions in face- and body-grooming, but there were also modest reductions in scratching. These results confirm that 8-OH-DPAT has a suppressant effect on all aspects of grooming, except where there are probable floor effects, and that this is independent of response competition from increased eating.

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding.