Characterization of new topical ketoprofen formulations prepared by drug entrapment in solid lipid matrices.

This paper describes the evaluation of a new pharmaceutical formulation based on ketoprofen entrapment in a solid lipid particle (SLP) matrix. The drug-SLP samples, which were elaborated using a processing technology based on supercritical CO(2) , consisted of a model of a controlled-release system for topical applications. Some of the samples contained silanized TiO(2) as an additional ingredient to increase the interaction between drug and lipid matrix. The study of the sample features relied on reversed-phase high-performance liquid chromatography with a C(18) column and ultraviolet spectroscopic detection at 266 nm. Characterization assays comprised the determination of the overall amount of ketoprofen in the samples, the assessment of the release-permeation kinetic profiles, and the evaluation of impurities and decomposition products. The release and permeation of encapsulated ketoprofen were assayed at 32°C and pH 6.8 by using a static diffusion cell. Results showed a sustained drug delivery for at least 24 h. Besides, no degradation species were detected throughout the release-permeation processes, which indicated that the stability of the drug in the SLP system was preserved.

Development of a polymeric patch impregnated with naproxen as a model of transdermal sustained release system.

This paper describes the preparation and characterization of transdermal patches impregnated with naproxen. A mixture of ethylene vinyl acetate and Eudragit E100 (80:20, w/w) is used as a polymeric matrix to obtain a thin membrane to be impregnated. Drug impregnation is carried out under pressurized CO(2) as a processing medium according to a two-step procedure. The patch is first soaked at 1000 psi and 22 °C for 2 h, and then foamed as a result of the rapid release of CO(2) pressure in order to increase the porosity of the surface. Subsequently, the naproxen solution is placed in contact with the membrane and then soaked in CO(2) at 450 psi and 37 °C for 2.5 h to enhance the mass transfer of drug into the polymer matrix. The characterization of the resulting samples by liquid chromatography, microscopy, and calorimetry provides information on naproxen content and distribution. Patches synthesized in this way are loaded with about 1% naproxen. The drug release and diffusion process through a membrane have been studied chromatographically using a Franz diffusion cell. Results have shown that a sustained delivery for more than 24 h is obtained.

Characterization of azacytidine/poly(L-lactic) acid particles prepared by supercritical antisolvent precipitation.

A controlled azacytidine release system based on drug encapsulation with a polymer material has been prepared and characterized. The drug systems were prepared by precipitation from solutions, using supercritical CO2 antisolvent technique operating in a semi-continuous mode. Azacytidine was dissolved in dimethylsulfoxide and poly-lactic acid in methylene chloride. The two solutions were mixed before being sprayed into the supercritical reactor. Experimental conditions were 40 degrees C for temperature, 11 MPa for pressure, and a CO2 flow rate of 30 ml min(-1). The precipitated drug-polymer particles were further characterized to determine the percentage of encapsulated drug and establish the delivery kinetics under various release conditions. A sustained delivery of the drug over a period of various hours was obtained. Besides, an improved stability of the coated drug with respect to the pure azacytidine was found, thus proving the suitability of this approach for dealing with unstable compounds.

Spectroscopic and chromatographic characterization of triflusal delivery systems prepared by using supercritical impregnation technologies.

This study describes the development and evaluation of an analytical method for the characterization of triflusal (2-acetoxy-4-(trifluoromethyl) benzoic acid) dispersed in sustained delivery systems prepared using supercritical fluid impregnation technology. Characterization assays comprised the determination of the percentage of triflusal and its degradation product impregnated in polymeric supports and further monitoring of the releases of the two drug components over time in physiological conditions. Preliminary delivery profiles were monitored spectrophotometrically using a continuous-flow system. In this case, no selective wavelength for discriminating between triflusal and metabolite was found so that measurements at 225 nm provided overall profiles corresponding to the two compounds. For a more accurate study, a chromatographic method was developed for monitoring the evolution of the concentration of the two components independently. Triflusal and metabolite were separated in a C(18) column and 25 mM acetic acid/acetate (pH 5.0)+methanol (40/60v/v) mobile phase. Several triflusal-polymer samples were prepared under different experimental conditions and release features were evaluated. Excellent delivery systems were obtained with poly(methyl)methacrylate beads treated at 40 degrees C and 190 bar for 48 h using supercritical carbon dioxide as a solvent. These samples showed a constant sustained release of drug for several weeks.

Characterization of acid-base properties of unstable drugs using a continuous-flow system with UV-vis spectrophotometric detection.

In this paper, we propose a continuous-flow system for the study of the acid-base characteristics of unstable drugs. 5-Azacytidine has been selected as a first model of unstable compound, which progressively decomposes in aqueous solutions. Besides, other compounds undergoing hydrolysis and oxidation side reactions have been also analyzed to explore the performance of the method. In comparison with conventional batch titrations, the drug decomposition can be minimized by the continuous renewal of the analyte solution. The composition of the buffer mixture is varied on-line during the process from successive changes in the flow rates of acid and basic stock solutions. As a result, the pH value of the test solution is varied in a controlled manner in the range of 1-13. Multivariate curve resolution based on alternating least squares has been used to extract relevant information concerning the acid-base properties of analytes. Results from the continuous-flow system have been compared with those obtained, using batch spectrophotometric titrations, and in the case of fast degradations, the performance of the proposed procedure has been superior.

Study of the degradation of 5-azacytidine as a model of unstable drugs using a stopped-flow method and further data analysis with multivariate curve resolution.

A general strategy for the study of degradation processes of drugs based on stopped-flow monitoring in a flow system is proposed. The flow system consists of a two-channel manifold for pumping sample and buffer solutions, which join and mix in a PTFE coil (57 cm x 0.7 mm i.d). The flow is stopped when the sample reaches the detection cell and, then, the corresponding kinetic processes are monitored in the spectral range 200-300 nm using a UV-vis diode array spectrophotometer. 5-Azacytidine has been chosen as a model of unstable drugs to illustrate the possibilities of the procedure. Kinetic runs have been developed at temperatures in the range 25-80 degrees C and pH values from 2 to 11 in order to investigate the influence of these factors on the degradation of the pharmaceutical agent. Multivariate curve resolution based on alternating least squares has been used for the data treatment in order to obtain the kinetic and spectral profiles of species involved in the degradation as well as to calculate the kinetic constants. Results indicate that 5-azacytidine is moderately stable in acid solutions while quickly decomposes in alkaline media. In addition, the degradation is dramatically accelerated with increasing temperature.