Development and Optimization of a Starch-Based Co-processed Excipient for Direct Compression Using Mixture Design.

The development of novel excipients with enhanced functionality has been explored using particle engineering by co-processing. The aim of this study was to improve the functionality of tapioca starch (TS) for direct compression by co-processing with gelatin (GEL) and colloidal silicon dioxide (CSD) in optimized proportions. Design of Experiment (DoE) was employed to optimize the composition of the co-processed excipient using the desirability function and other supporting studies as a basis for selecting the optimized formulation. The co-processed excipient (SGS) was thereafter developed by the method of co-fusion. Flow and compaction studies of SGS were carried out in comparison to its parent component (TS) and physical mixture (SGS-PM). Tablets were prepared by direct compression (DC) containing ibuprofen (200 mg) as a model for poor compressibility using SGS, Prosolv®, and StarLac® as multifunctional excipients. The optimized composition of SGS corresponded to TS (90%), GEL (7.5%), and CSD (2.5%). The functionality of SGS was improved relative to SGS-PM in terms of flow and compression. Tablets produced with SGS were satisfactory and conformed to USP specifications for acceptable tablets. SGS performed better than Prosolv® in terms of disintegration and was superior to StarLac with respect to tensile strength and disintegration time. The application of DoE was successful in optimizing and developing a starch-based co-processed excipient that can be considered for direct compression tableting.

Effects of cooling rate in microscale and pilot scale freeze-drying - Variations in excipient polymorphs and protein secondary structure.

Microscale freeze-drying makes rapid process cycles possible for early-stage formulation development. To investigate the effects of equipment scale and cooling rate on the solid state properties and the protein's secondary structure of a sample, three binary formulations of catalase were prepared and freeze-dried with sucrose, mannitol, or (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD). The protein's secondary structure was assessed using attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR). The solid state properties were assessed using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The results were interpreted with respect to the biological activity of catalase after its reconstitution. According to the results of both the protein secondary structure and the reconstituted biological activity, scale-up could be achieved with the sucrose-catalase formulation when it was prepared at a high cooling rate and with the mannitol-catalase formulation when prepared at a low cooling rate. However, differences in the polymorph composition of crystalline mannitol were noted. No cooling rate influence was found with the HP-ß-CD formulation. The results clearly indicate that the effects of the cooling rate should be closely examined during microscale formulation development and scale-up of the freeze-drying process.

Analytical techniques for characterization of cyclodextrin complexes in the solid state: A review.

Cyclodextrins are cyclic oligosaccharides able to form inclusion complexes with a variety of hydrophobic guest molecules, positively modifying their physicochemical properties. A thorough analytical characterization of cyclodextrin complexes is of fundamental importance to provide an adequate support in selection of the most suitable cyclodextrin for each guest molecule, and also in view of possible future patenting and marketing of drug-cyclodextrin formulations. The demonstration of the actual formation of a drug-cyclodextrin inclusion complex in solution does not guarantee its existence also in the solid state. Moreover, the technique used to prepare the solid complex can strongly influence the properties of the final product. Therefore, an appropriate characterization of the drug-cyclodextrin solid systems obtained has also a key role in driving in the choice of the most effective preparation method, able to maximize host-guest interactions. The analytical characterization of drug-cyclodextrin solid systems and the assessment of the actual inclusion complex formation is not a simple task and involves the combined use of several analytical techniques, whose results have to be evaluated together. The objective of the present review is to present a general prospect of the principal analytical techniques which can be employed for a suitable characterization of drug-cyclodextrin systems in the solid state, evidencing their respective potential advantages and limits. The applications of each examined technique are described and discussed by pertinent examples from literature.

Tomografía de coherencia óptica de segunda generación en la práctica clínica. La adquisición de datos de alta velocidad muestra una reproducibilidad excelente en pacientes tratados con intervenciones coronarias percutáneas / Second-generation optical coherence tomography in clinical practice. High-speed data acquisition is highly reproducible in patients undergoing percutaneous coronary intervention

Introducción y objetivos. Se ha desarrollado una segunda generación de sistemas de tomografía de coherencia óptica (OCT) (dominio de Fourier, OCT-DF) que permiten las retiradas a alta velocidad sin necesidad de ocluir transitoriamente la arteria coronaria durante la obtención de imágenes. El objetivo de este estudio es evaluar la reproducibilidad de los sistemas de OCT-DF para la caracterización de la placa y la evaluación de la implantación del stent en pacientes a los que se practican intervenciones coronarias percutáneas. Métodos. Entre mayo y diciembre de 2008, se incluyó en el estudio a 45 pacientes para los que se había programado una intervención coronaria percutánea. La adquisición de la OCT-DF se realizó con una técnica no oclusiva con velocidades de retirada de entre 5 y 20 mm/s. Se evaluó la reproducibilidad entre estudios, entre observadores y en el observador para la caracterización de la placa y el análisis de los stents. Resultados. La obtención de imágenes de dominio de Fourier se realizó satisfactoriamente en todos los pacientes (n = 45). El ritmo de infusión medio fue de 3 ± 0,4 ml/s y el volumen de contraste por retirada, 16,1 ± 3,5 ml. La media de duración y longitud de la retirada fue de 3,2 ± 1,2 s y 53,3 ± 12,4 mm. La reproducibilidad entre estudios, en cuanto a la visualización de la disección del borde, el prolapso tisular, la disección en el stent y la mala aposición, fue excelente (k = 1). Los valores de kappa para la coincidencia entre estudios, entre observadores y en el observador en la caracterización de la placa fueron 0,92, 0,82 y 0,95 respectivamente. Conclusiones. La tecnología de OCT de segunda generación, que obtiene datos a alta velocidad, muestra buena reproducibilidad entre estudios, entre observadores y en el observador para la caracterización de la placa y evaluar la implantación del stent en pacientes a los que se practican intervenciones coronarias percutáneas (AU)

Introduction and objectives. The development of second-generation optical coherence tomography (i.e. Fourier domain optical coherence tomography, FD-OCT) has made it possible to perform high speed pullbacks during image acquisition without the need for transient occlusion of the coronary artery. The objective of this study was to assess the reproducibility of FD-OCT systems for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention. Methods. The study included 45 patients scheduled for percutaneous coronary intervention who were enrolled between May and December 2008. Image acquisition was performed by FD-OCT using a non-occlusive technique and employing pullback speeds ranging from 5 to 20 mm/s. Interstudy, interobserver and intraobserver reproducibility of plaque characterization and stent analysis were assessed. Results. Fourier domain imaging was successfully performed in all patients (n=45). The average flush rate was 3±0.4 mL/s and the contrast volume per pullback was 16.1±3.5 mL. The mean pullback duration and length were 3.2±1.2 s and 53.3±12.4 mm, respectively. The interstudy reproducibility for visualizing edge dissection, tissue prolapse, intrastent dissection and malapposition was excellent (k=1). The kappa values for interstudy, interobserver and intraobserver agreement on plaque characterization were 0.92, 0.82 and 0.95, respectively. Conclusions. A second-generation OCT system (i.e. FD-OCT) involving high-speed data acquisition demonstrated good interstudy, interobserver and intraobserver reproducibility for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention (AU)

Trends in Fourier transform infrared spectroscopic imaging.

Fourier transform infrared (FTIR) spectroscopic imaging is a relatively new method that has received great attention as a new field of analytical chemistry. The greatest benefit of this technique lies in the high molecular sensitivity combined with a spatial resolution down to a few micrometers. Another advantage is the ability to probe samples under native conditions, which allows new insights into samples without the need for fixation, stains, or an additional marker. Advances in instrumentation have made FTIR spectroscopic imaging the tool of choice for an increasing number of applications. The main applications are in the bioanalytical chemistry of cells and tissue, polymers, and recently as well as in homeland security. This report gives a short overview of current developments and recent applications.

Electron capture dissociation implementation progress in Fourier transform ion cyclotron resonance mass spectrometry.

Successful electron capture dissociation (ECD) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) applications to peptide and protein structural analysis have been enabled by constant progress in implementation of improved electron injection techniques. The rate of ECD product ion formation has been increased to match the liquid chromatography and capillary electrophoresis timescales, and ECD has been combined with infrared multiphoton dissociation in a single experimental configuration to provide simultaneous irradiation, fast switching between the two techniques, and good spatial overlap between ion, photon, and electron beams. Here we begin by describing advantages and disadvantages of the various existing electron injection techniques for ECD in FT-ICR MS. We next compare multiple-pass and single-pass ECD to provide better understanding of ECD efficiency at low and high negative cathode potentials. We introduce compressed hollow electron beam injection to optimize the overlap of ion, photon, and electron beams in the ICR ion trap. Finally, to overcome significant outgassing during operation of a powerful thermal cathode, we introduce nonthermal electron emitter-based electron injection. We describe the first results obtained with cold cathode ECD, and demonstrate a general way to obtain low-energy electrons in FT-ICR MS by use of multiple-pass ECD.

Nucleic Acid analysis by fourier transform ion cyclotron resonance mass spectrometry at the beginning of the twenty-first century.

Mass spectrometers measure an intrinsic property (i.e., mass) of a molecule, which makes it an ideal platform for nucleic acid analysis. Importantly, the unparalleled capabilities of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry further extend its usefulness for nucleic acid analysis. The beginning of the twenty-first century has been marked with notable advances in the field of FT-ICR mass spectrometry analysis of nucleic acids. Some of these accomplishments include fundamental studies of nucleic acid properties, improvements in sample clean up and preparation, better methods to obtain higher mass measurement accuracy, analysis of noncovalent complexes, tandem mass spectrometry, and characterization of peptide nucleic acids. This diverse range of studies will be presented herein.

The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR.

The purpose of this paper is to show how the utilization of Fourier Transform Infrared (FTIR) spectroscopy can be interesting in stability studying of cosmetic or pharmaceutical "oil in water" (O/W) emulsions. In this study temperature storage tests were performed to accelerate the aging process and evaluate the stability of five emulsions. Emulsions were analyzed by FTIR and classical methods (conductivity, viscosity, pH, texture analysis) in order to determine a method that would enable predicting the emulsion's stability. During the aging process, modifications of chemical functions are measured by FTIR (using spectrometric indices), such modifications included: a decrease of unsaturation index, an increase of carbonyl index and a broadening of the carbonyl band. This band was deconvoluted to evaluate the contribution of different species in the broadening phenomenon, which seems to be caused by the appearance of free fatty acids. Conductimetry seems to be the most sensitive technique to assess physical modifications during emulsion's aging. Concerning the most unstable emulsions, a progressive increasing of conductivity was observed several months before the emulsion destabilizes. Consequently, FTIR and conductimetry are two complementary techniques. Conductimetry is a useful technique to predict emulsion destabilization while FTIR allows the measurement of chemical modifications and helps to understand the chemical mechanisms which occur during the oxidation.

FTICR mass spectrometry for qualitative and quantitative bioanalyses.

Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is playing an increasing role in the characterization of cellular systems owing to its capabilities for providing higher confidence of identification, increased dynamic range and sensitivity unmatched by other MS platforms. Particularly in proteomics, where global and quantitative approaches are essential, the attributes of FTICR-MS are poised to make significant contributions. Recent advances in the field that have particular importance for proteomic applications include the use of high-performance micro-capillary column separation techniques coupled to FTICR, as well as methods that improve protein identification, sensitivity, dynamic range and throughput.

Carbonyl metallo immuno assay: a new application for Fourier transform infrared spectroscopy.

We describe here the development of a new, non-isotopic immunological assay termed CMIA (carbonyl metallo immunoassay) that uses metal carbonyl complexes as tracers and Fourier transform infrared spectroscopy (FT-IR) as the detection method. This assay is based on the particular spectral features of these complexes, which show very strong absorption bands in the 1,800-2,200 cm(-1) spectral range where proteins and organic molecules do not absorb. In Section 1, the optimisation of the quantitative detection of these tracers is detailed. In Section 2, the implementation of mono-CMIA is described, including the CMIA assays of three antiepileptic drugs (carbamazepine, phenobarbital, phenytoin). Finally, extension to the simultaneous double- and triple-CMIA of these drugs is reported.

Orientational order determination by internal reflection infrared spectroscopy.

PATIR-FTIR spectroscopy is a powerful technique for the determination of molecular order in thin films such as supported lipid membranes, but it relies on electromagnetic theory which is incomplete and potentially misleading. A complete derivation of the current theory for two, three and four phase system has been reported. The two phase and thin film approximations most commonly used in practice have been shown to represent the thickness-dependent expressions from which they are derived with a high degree of accuracy. However, these expressions are based on the macroscopic behavior of dielectric materials, and may not be accurate when applied to microscopic circumstances. The potential error introduced is qualitatively and quantitatively significant. Further experimental and theoretical work is needed to verify the accuracy of this theory, or to refute and refine it. This effort to do this is warranted by the power and increasing popularity of the technique.