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.

Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces

Freeze-dried (lyophilised) wafers and solvent cast films from sodium alginate (ALG) and sodium carboxymethylcellulose (CMC) have been developed as potential drug delivery systems for mucosal surfaces including wounds. The wafers (ALG, CMC) and films (CMC) were prepared by freeze-drying and drying in air (solvent evaporation) respectively, aqueous gels of the polymers containing paracetamol as a model drug. Microscopic architecture was examined using scanning electron microscopy, hydration characteristics with confocal laser scanning microscopy and dynamic vapour sorption. Texture analysis was employed to investigate mechanical characteristics of the wafers during compression. Differential scanning calorimetry was used to investigate polymorphic changes of paracetamol occurring during formulation of the wafers and films. The porous freeze-dried wafers exhibited higher drug loading and water absorption capacity than the corresponding solvent evaporated films. Moisture absorption, ease of hydration and mechanical behaviour were affected by the polymer and drug concentration. Two polymorphs of paracetamol were observed in the wafers and films, due to partial conversion of the original monoclinic to the orthorhombic polymorph during the formulation process. The results showed the potential of employing the freeze-dried wafers and solvent evaporated films in diverse mucosal applications due to their ease of hydration and based on different physical mechanical properties exhibited by both type of formulations.

Raman spectroscopy in pharmaceutical analysis

A wide and versatile range of analytical techniques are routinely used, indeed are necessary, in pharmaceutical analysis. Over the past decade Raman spectroscopy has increasingly come to the fore as a valuable member of the arsenal of methods used, from both a fundamental and applied perspective, for the interrogation of solid, liquid and solution phase samples. Advances have occurred not only in instrumentation but also in fundamental techniques and applications. The method holds substantial potential for the investigation of, what are normally considered, problematic or challenging areas of analysis. The aforementioned areas include – but are, definitely not limited too reaction kinetics, pharmaceutical drug discovery, detection of counterfeit/adulterated/illegal drugs, trace analysis and uses for on-line pharmaceutical process manufacturing. This, the first of several articles on the use of Raman spectroscopic techniques in pharmaceutical analysis, provides an introductory overview of the theory of the technique.

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.

The application of electrostatic dry powder deposition technology to coat drug-eluting stents

Purpose: A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles. Methods: Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces. Results: The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion. Conclusions: EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.