An overview of the analytical characterization of nanostructured drug delivery systems: Towards green and sustainable pharmaceuticals: A review

The analytical characterization of drug delivery systems prepared by means of green manufacturing technologies using CO₂ as a processing fluid is here reviewed. The assessment of the performance of nanopharmaceuticals designed for controlled drug release may result in a complex analytical issue and multidisciplinary studies focused on the evaluation of physicochemical, morphological and textural properties of the products may be required. The determination of the drug content as well as the detection of impurities and solvent residues are often carried out by chromatography. Assays on solid state samples relying on X-ray, vibrational and nuclear magnetic resonance spectroscopies are of great interests to study the composition and structure of pharmaceutical forms. The morphology and size of particles are commonly checked by microscopy and complementary chemical information can be extracted in combination with spectroscopic accessories. Regarding the thermal behavior, calorimetric and thermogravimetric techniques are applied to assess the thermal transitions and stability of the samples. The evaluation of drug release profiles from the nanopharmaceuticals can be based on various experimental set-ups depending on the administration route to be considered. Kinetic curves showing the evolution of the drug concentration as a function of time in various physiological conditions (e.g., gastric, plasmatic or topical) are recorded commonly by UV–vis spectroscopy and/or chromatography. Representative examples are commented in detail to illustrate the characterization strategies.     

Determination of biogenic amines in wines by pre-column derivatization and high-performance liquid chromatography coupled to mass spectrometry

A new HPLC method for determining biogenic amines in wines is developed. This method is based on pre-column amine derivatization, further separation of derivatives and on-line hyphenation of HPLC to atmospheric pressure chemical ionization mass spectrometry (APCI-MS). Biogenic amines have been derivatized with 1,2-naphthoquinone-4-sulfonate at 65 °C and pH 9.2 for 5 min. The separation of derivatives has been accomplished in a C₁₈ analytical column using an elution gradient based on increasing the percentage of methanol. Derivatives have been ionized in positive mode and detected by selected ion monitoring. The operating conditions of the APCI-MS system (voltages, temperatures and gases) have been thoroughly optimized to obtain the maximum sensitivity for all analytes. In the selected conditions, APCI-MS spectra display little fragmentation and good signal-to-noise ratio. Depending on the amine characteristics, the main spectral peaks are due to mono- and di-derivative products. Figures of merit of the method have been established under the selected conditions using red wine samples. Recoveries ranging from 94% to 106% have been obtained which prove excellent accuracy of the method in the determination of histamine, putrescine, cadaverine, tryptamine, phenylethylamine, tyramine and serotonin in red wines. The proposed method has been applied to the analysis of commercial wines from different Spanish regions.     

A novel solventless coating method to graft low‐molecular weight polyethyleneimine on silica fine powders

The overall objective of the present study was to modulate the surface characteristics of aerogel‐like submicron and nanometric particles by coating them with polyethyleneimine (PEI) to suit specific biological applications. A new process for the covalent grafting of low‐molecular weight PEI chains has been described, based on the use of compressed CO₂ as the initiator of the ring opening polymerization of the ethyleneimine monomer, which was performed in the presence of silica particles. Coating was done at low pressure and temperature and in the absence of any organic solvent. Obtained materials were compared with a product prepared following the standard soaking procedure for PEI coating. Materials were characterized regarding composition, structure, surface charge, particle size, morphology, and drug release. The developed process led to the covalent grafting of low‐molecular weight PEI on the silica surface, which conferred an increased thermal stability for the coating and low cytotoxicity to the particles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2760–2768     

Continuous flow derivatization system coupled to capillary electrophoresis for the determination of amino acids

A derivatization system coupled to capillary electrophoresis for the determination of amino acids using 1,2-naphthoquinone-4-sulfonate as a labeling agent is described. In this system, amino acids are derivatized on-line in a three-channel flow manifold for sample, reagent and buffer solutions. The reaction takes place in a PTFE coil heated at 80 degrees C. The resulting solution, which contains the amino acid derivatives, is introduced into the electrophoretic system by means of an appropriate interface. Subsequently, amino acid derivatives are separated at 25 kV using a 40 mM sodium tetraborate aqueous solution with 30% (v/v) isopropanol solution as a running buffer. The electropherograms are monitored spectrophotometrically at 230 nm. The method has been applied to the determination of amino acids in feed samples and pharmaceutical preparations. A good concordance of the predicted values with those given by a standard amino acid analyzer is shown.     

Flow-Injection Differential Spectrophotometric pH Selectivity System for the Determination of Cyclamate Contaminants

A flow-injection system with differential spectrophotometric detection is proposed for the simultaneous determination of aniline and cyclohexylamine based on their reaction with 1,2-naphthoquinone-4-sulfonate (NQS). The pH is chosen to achieve selectivity since only aniline reacts at acidic pH whereas the two amines are derivatized in basic medium. The flow manifold comprises two reactors and two detection cells for developing and monitoring the reaction under selective and general (non-selective) conditions. A double beam spectrophotometer is used for differential detection, with two flow cells placed in the sample and reference holders. Figures of merit such as sensitivity, linear range, detection limit and precision are established. The evaluation of accuracy using a series of synthetic mixtures indicates overall prediction errors of 3% and 5% for aniline and cyclohexylamine, respectively. The method is applied to the determination of amine impurities in commercial sweeteners. Good concordance between the proposed and the standard chromatographic methods is found.     

Crystallization Kinetics of Polypropylene-polyethylene-based Copolymers

A crystallization kinetics analysis of several polypropylene-polyethylene (PP-PE), PP-rich copolymers was made by means of differential scanning calorimetry. The crystallization was studied via calorimetric measurements at different cooling rates. Several additives were added to the base material. Some test samples were subjected to artificial ageing processes. A modified isoconversional method was used to describe the crystallization process under non-isothermal conditions. The value of the Avrami parameter was determined for primary and secondary crystallization. This revised version was published online in August 2006 with corrections to the Cover Date.     

Flow-injection determination of zidovudine in plasma samples using multivariate curve resolution

This paper describes a spectrophotometric flow-injection method for the determination of an antiretroviral drug (zidovudine) in plasma samples. The main goal of this study is the development of feasible analytical method to monitor the plasmatic drug levels in a rapid and simple way as an alternative to chromatographic procedures. The flow-injection system proposed consists of a two-channel manifold with the injection of the sample into an acid carrier and on-line generation of a pH-gradient. The corresponding data are monitored over time using a diode array spectrophotometer. The discrimination of zidovudine species from plasma components is accomplished through chemometric data analysis based on the zidovudine features on both spectral and time domains. A pretreatment procedure consisting of liquid-liquid extraction is used for sample clean-up. However, despite the pretreatment, noticeable amounts of unknown substances acting as interferences are still present in the extracts. As relevant analytical parameters, the analyte recovery in the extraction process is 101% at 5.3 μg mL⁻¹ and the detection limit is 0.013 μg mL⁻¹. Multivariate curve resolution with alternating least squares is used to recover the analyte profiles for its further determination. As a result, the quantification of zidovudine in plasma can be accomplished even in the presence of plasma components with overall prediction error below 3%.     

Compressed antisolvent process for polymer coating of drug-loaded aerogel nanoparticles and study of the release behavior

The overall objective of the present work was to modulate the release behavior of drug-impregnated silica particles from almost instantaneous release to a more sustained delivery, prolonged during several hours. Triflusal was chosen as a model drug of the low biodisponibility type. The process is based in the coating with Eudragit® RL 100 polymer of aerogel-like silica particles. Materials were processed in compressed CO₂ by using the batch and semicontinuous antisolvent coating methods. Triflusal release from Eudragit-coated aerogel particles was compared with the dissolution profiles recorded for pristine triflusal and for triflusal impregnated into polymer or non-coated aerogel particles. The release profiles were determined by high-performance liquid chromatography. Eudragit-coated materials presented an intermediate drug-release rate between this obtained for the infused polymer and that of the impregnated aerogel particles. Diffusion-governed mechanisms were found for the studied aerogel-like systems after fitting the release data to both Korsmeyer-Peppas and Baker-Lonsdale equations. The major advantage of the compressed CO₂ antisolvent approach was the ability to physically coat very fine particles (<100 nm). Moreover, the stability of the studied drug in water increased after coating. Figure

Schematic representation of the antisolvent CO₂ particle coating and release behavior of the obtained hybrid products     

DSC Study of the Effects of High Pressure and Spray-Drying Treatment on Porcine Plasma

One use of blood generated in abattoirs is to obtain dehydrated plasma which can be used as a functional ingredient in the preparation of foods. High hydrostatic pressure is a new technique for improvement of the sanitary quality of food products or their ingredients. The changes caused in the proteins by treatment can affect their functional properties, and differential scanning calorimetry DSC was therefore applied to detect possible conformational changes in the plasma proteins. The DSC results in the present study show that spray-drying does not appreciably affect the protein structure, but high-pressure treatment seems to have a denaturing effect. This revised version was published online in July 2006 with corrections to the Cover Date.