Biomedical subjects

Staffan Folestad

Publications and source records attributed to Staffan Folestad.

9 recordsLinked to original sources

PubMed2005

Characterization of different laser irradiation methods for quantitative Raman tablet assessment.

Quantitative Raman spectroscopy of conventional wet granulated pharmaceutical immediate release tablets and subsequent data evaluation was investigated. Different aspects of quantitative assessment of active pharmaceutical ingredient (API) in intact tablets with special focus on sub-sampling issues were addressed. Four different geometric laser irradiance patterns were examined to study the effect of sub-sampling within the tablets. The Raman data was evaluated using both univariate and multivariate techniques. UV absorbance spectroscopy was used as a reference method. The best result in terms of prediction error was attained by irradiating a large area of the tablets. Using multivariate calibration with multiplicative signal correction (MSC) the prediction error was 1.7%. In addition, the effect of tablet density on the Raman assessment was investigated. It was found that quantitative Raman assessment of chemical content can be made insensitive to variations in tablet density corresponding to a manufacturing compression interval of 5-20 kN provided that adequate data treatment is used. A short discussion about sample heating in the context of different irradiation patterns is included with reference to previous work. In conclusion, the present study provides a platform for developing an implementation strategy for quantitative Raman spectroscopy for both laboratory analysis and process analytical technology (PAT) applications.

Calibration↗

PubMed2005

Time-resolved NIR spectroscopy for quantitative analysis of intact pharmaceutical tablets.

Near-infrared (NIR) spectroscopy is a useful technique for quantitative measurements of intact tablets, but it suffers from limitations due to the fact that changes in the physical properties of a sample strongly affect the recorded spectrum. In this work, time-resolved transmission NIR spectroscopy was utilized to conduct quantitative measurements of intact tablets. The technique enables separation of the absorption properties of the sample from the scattering properties and can therefore handle changes of the physical parameters of the samples in a better way than conventional NIR transmission spectroscopy. The experiments were conducted using a pulsed Ti:sapphire laser coupled into a nonlinear photonic crystal fiber as light source. The light transmitted through the sample was measured by a time-resolving streak camera. A comparison of the results from the time-resolved technique with the results from conventional transmission NIR spectroscopy was made using tablets containing different concentrations of iron oxide and manufactured with different thicknesses. A PLS model made with data from the time-resolved technique predicted samples 5 times better than a PLS model made data from the conventional NIR transmission technique. Furthermore, an improvement to predict samples with physical properties outside those included in the calibration set was demonstrated.

Calibration↗

PubMed2005

Evaluation of basic algorithms for transferring quantitative multivariate calibrations between scanning grating and FT NIR spectrometers.

A key issue in near infrared spectroscopy (NIR) is the possibility to use calibrations generated on one instrument for predictions on others. A number of methods for calibration transfer have been proposed, but which method to choose is typically not straightforward. An evaluation of a number of methods for transferring quantitative calibrations between different instruments was carried out on near infrared diffuse-reflectance data from a pharmaceutical formulation. Six instruments were included in the study, five of which were scanning grating instruments, both with and without fibre-optic probe configuration, and one of which was a Fourier-transform instrument, equipped with a fibre-optic probe. The results show that it is possible to transfer calibrations between different instruments, provided that a structured procedure is used. Simple techniques for calibration transfer, such as slope/bias correction on the predicted results, as well as standard normal variate transformation and local centring of the raw spectra, gave considerably lower prediction errors on transfer than did standardisation with a certified diffuse-reflectance standard, or direct transfer without any transfer function. Notably, including more than one instrument in the calibration also improved the prediction ability of the models on calibration transfer. No significant differences in wavelength scale were found when a certified diffuse-reflectance wavelength standard was measured on the instruments studied. Nor did simulated wavelength scale differences below +/-0.3 nm cause any significant change in the prediction errors.

Algorithms↗

PubMed2005

Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions.

Capillary electrophoresis (CE) was evaluated as an in-vitro format for experimental modelling of membrane permeability using only nanogram quantities of drug compounds. The rationale for the CE technique emanates from emulation of a lipid-like pseudo-stationary phase that governs separations mainly as a result of differences in molecular size, lipophilicity, hydrogen bonding and charge, all of which also have a strong influence on in-vivo drug absorption. By means of micellar, microemulsion and liposome electrolytes, the migration behaviour was studied at 37 degrees C for 22 model drug compounds. The generated CE retention factor data were then compared with membrane permeability reference data. Both simple log D and more common Caco-2 cell parameters were evaluated. In addition, permeation through intestinal segments of rat ileum and rat colon was included. An improved correlation was obtained in the order: micellar < microemulsion < liposome systems. Although the correlation for the best liposome CE system was only R(2)=0.77, the evaluation results for all emphasized the strength and flexibility of CE for assessing specific drug-membrane interaction through tailor-made lipophilic media.

Animals↗

PubMed2005

Scatter correction of transmission near-infrared spectra by photon migration data: quantitative analysis of solids.

The scope of this work is a new methodology to correct conventional near-infrared (NIR) data for scattering effects. The technique aims at measuring the absorption coefficient of the samples rather than the total attenuation measured in conventional NIR spectroscopy. The main advantage of this is that the absorption coefficient is independent of the path length of the light inside the sample and therefore independent of the scattering effects. The method is based on time-resolved spectroscopy and modeling of light transport by diffusion theory. This provides an independent measure of the scattering properties of the samples and therefore of the path length of light. This yields a clear advantage over other preprocessing techniques, where scattering effects are estimated and corrected for by using the shape of the measured spectrum only. Partial least squares (PLS) calibration models show that, by using the proposed evaluation scheme, the predictive ability is improved by 50% as compared to a model based on conventional NIR data alone. The method also makes it possible to predict the concentration of active substance in samples with other physical properties than the samples included in the calibration model.

Algorithms↗

PubMed2004

Quaternary ammonium substituted agarose as surface coating for capillary electrophoresis.

A novel positively charged polymer of quaternary ammonium substituted agarose (Q-agarose) has been synthesized and explored for use as a coating in capillary electrophoresis. The fast and simple coating procedure is based on a multi-site electrostatic interaction between the polycationic agarose polymer and the negatively charged fused-silica surface. By simply flushing fused-silica capillaries with hot polymer solution a positively charged, hydrophilic deactivation layer is achieved. The polymer surface provides an intermediate electroosmotic flow of reversed direction, over a range of pH 2-11, compared to unmodified fused-silica. The coating procedure was highly reproducible with an RSD of 4%, evaluated as the electroosmotic flow mobility for 30 capillaries prepared at 10 different occasions. The application of Q-agarose coated capillaries in separation science was investigated using a set of basic drugs and model proteins and peptides. Due to the intermediate electroosmotic flow generated, the resolution of basic drugs could be increased, compared to using bare fused-silica capillaries. Moreover, the coating enabled separation of proteins and peptides with efficiencies up to 300.000 plates m(-1).

Electrophoresis, Agar Gel↗

PubMed2003

Determination of dissociation constants of labile drug compounds by capillary electrophoresis.

The utility of capillary electrophoresis (CE) for determination of the negative logarithm of dissociation constants (pK(a)) of labile compounds was investigated. In this study pyridinyl-methyl-sulfinyl-benzimidazoles (PMSB's), which have both an acidic and a basic pK(a), were selected as a first set of model drug compounds. This is a group of compounds that are known to degrade in aqueous solutions under neutral and acidic conditions which thus may impair their pK(a) determination when using common batch techniques based on spectrophotometry or potentiometry. An additional set of model drug compounds, benzenesulfonic acid phenethyloxy-phenyl esters (BSAP's), which are labile at high pH, were also studied. It is demonstrated that pK(a) values can be determined with high precision and accuracy by CE for both these sets of model compounds because decomposition products and impurities can be sufficiently separated from the main component. Based on the results in this study, a general strategy is proposed and discussed for determination of pK(a) for labile compounds. Key steps comprise use of a stabilizing sample diluent, injection by electromigration, short analysis time, and characterization of the main component by UV-Vis spectra.

Benzimidazoles↗

PubMed2003

In-situ near-infrared spectroscopy monitoring of the lyophilization process.

PURPOSE: The purpose of this work was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to monitor the freeze-drying process in-situ. METHODS: The experiment was performed in a pilot-scale freeze-dryer, in which the NIRS probe was interfaced using a lead-through to the lyophilizer. Special equipment for the sample presentation was developed. NIRS measurements were made using a FT (Fourier transform)-NIR spectrometer fitted with a single fiber reflectance probe. RESULTS: The physical changes, that is, freezing, sublimation, and desorption, generated significant spectral changes. There was good agreement between NIRS monitoring and product temperature monitoring about the freezing process and the transition from frozen solution to ice-free material. The NIRS monitoring also provided new information about the process that was not possible to detect with product temperature monitoring, such as the rate of the desorption process and the steady-state where the drying was complete. The NIRS monitoring yields significantly more information about the actual process and essentially explains the observed changes of the product temperature during the lyophilization process. CONCLUSIONS: NIRS monitoring is a viable tool for in-situ monitoring, both qualitatively and quantitatively. It can facilitate investigations of the drying process within a sample. The small volume monitored makes sample presentation very important.

Chemical Phenomena↗

PubMed2002

Method for immobilization of liposomes in capillary electrophoresis by electrostatic interaction with derivatized agarose.

A novel procedure for immobilization of liposomes inside fused-silica capillaries is demonstrated. First, the inner wall of the capillaries was coated with a positively charged polymer, composed of derivatized agarose. Subsequently, negatively charged liposomes were immobilized by electrostatic interaction on the polymer coating. The developed liposome coated capillaries were used as a nanoseparation tool for studying interactions between small drug compounds and liposomes. Part of this work was presented at the 15th International Symposium on Microscale Separations and Analysis, HPCE 2002, Stockholm, Sweden, April 2002.

Electrophoresis, Agar Gel↗