[Show abstract][Hide abstract] ABSTRACT: The purpose of the present work was to validate an accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection for the quantitative analysis of memantine hydrochloride. In order to analyze a molecule with no chromophoric groups that could be detected by a UV/visible detector, it was necessary to extract the drug and to perform a dansylation reaction that enabled the UV/visible detection of the derivatized molecule. Separation was carried out with a 150 mm Kromasil C18 column at room temperature. The detection response, at 218 nm, was found to be linear in the concentration range from 0.5 to 50 μg/mL. The method was validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness. The limit of detection (LOD) was 0.144 μg/mL, and the limit of quantification (LOQ) was 0.437 μg/mL. The dansylated memantine complex was stable for at least five days in all the conditions evaluated. The potential use of this method has been demonstrated by the quantification of memantine hydrochloride contained in samples from the study of its in vitro transdermal permeation.
[Show abstract][Hide abstract] ABSTRACT: The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2012; 82(1):164-70. DOI:10.1016/j.ejpb.2012.06.005 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pizotifen malate is an antihistamine and serotonin inhibitor used in the preventive treatment of migraine and eating disorders. A simple, rapid, accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection was validated for the quantitative analysis of pizotifen malate in samples from in vitro transdermal diffusion studies. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantification and robustness. Drug stability in the solution was also determined under different conditions. Separation was carried out using a 250 × 4.0 mm Kromasil(®) C(18) column at room temperature. The detector response, fitted at 254 nm, was found to be linear in a concentration range between 0.24 and 24.0 µg/mL. The limit of detection was 0.02 µg/mL and the limit of quantification was 0.07 µg/mL. Finally, in vitro transdermal diffusion of pizotifen malate was characterized using the validated HPLC method.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present work was to characterize the in vitro transdermal absorption of almotriptan through pig ear skin. The passive diffusion of almotriptan malate and its iontophoretic transport were investigated using current densities of 0.25 and 0.50mA/cm(2). In vitro iontophoresis experiments were conducted on diffusion cells with an agar bridge without background electrolytes in the donor compartment. Although both current densities applied produced a statistically significant increment with respect to passive permeation of almotriptan (p<0.01), that of 0.50mA/cm(2) proved to be the best experimental condition for increasing the transport of almotriptan across the skin. Under these experimental conditions, the transdermal flux of the drug increased 411-fold with respect to passive diffusion, reaching 264±24μg/cm(2)h (mean±SD). Based on these results, and taking into account the pharmacokinetics of almotriptan, therapeutic drug plasma levels for the management of migraine could be achieved via transdermal iontophoresis using a reasonably sized (around 7.2cm(2)) patch.
International Journal of Pharmaceutics 09/2011; 416(1):189-94. DOI:10.1016/j.ijpharm.2011.06.039 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nadolol and propranolol are beta-blockers used to prevent the onset of migraines. Two simple and rapid High Performance Liquid Chromatographic (HPLC) methods with ultraviolet detection were evaluated in order to establish their efficacy for detecting nadolol and propranolol hydrochloride in samples obtained from in vitro transdermal absorption studies. Both methods were validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification and robustness. Moreover, the stability of both drugs in a buffered solution was assessed. Separation was carried out on a 250 mm Kromasil® C18 column at room temperature. When nadolol was analysed, the detector response at 269 nm was found to be linear in a concentration range of 0.17 to 167 μM. In the case of propranolol hydrochloride, a fixed wavelength of 291 nm for quantification corresponded with calibration lines in the range of 0.11 to 113 μM. The limits of detection (LOD) and quantification (LOQ) were 0.058 and 0.038 μM and 0.171 and 0.115 μM for nadolol and propranolol hydrochloride, respectively. The maximum relative error and relative standard deviation detected were 5.19% and 6.08% respectively for nadolol and 3.57% and 6.44% respectively for propranolol hydrochloride. The results of robustness were highly satisfactory.
Current Pharmaceutical Analysis 05/2011; 7(2-2):79-87. DOI:10.2174/157341211795684862 · 0.72 Impact Factor