Biomedical subjects

T R M De Beer

Publications and source records attributed to T R M De Beer.

5 recordsLinked to original sources

PubMed2006

Influence of particle size on the quantitative determination of salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy.

A second order polynomial calibration model was developed and statistically validated for the direct and non-destructive quantitative analysis - without sample preparation - of the active pharmaceutical ingredient (API) salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy. The calibration curve was modeled by plotting the peak intensity of the vector normalized spectral band between 757 and 784cm(-1) against the known salicylic acid concentrations in standards. At this band, no spectral interferences from the ointment vehiculum (white vaseline) are observed. For the validation of the polynomial model, its fit and its predictive properties were evaluated. The validated model was used for the quantification of 25 ointments, compounded by different retail pharmacists. The same standards and samples were used, both for development and validation of a regression model and for quantitative determination by HPLC - with sample preparation - as described for the related substances of salicylic acid in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the HPLC results (p=0.22), provided that the particle size of salicylic acid in the standards is the same as in the analyzed samples. The non-destructive FT-Raman method is a reliable alternative for the destructive HPLC method, as it is faster and does not require sample pre-treatment procedures.

Calibration↗

PubMed2006

Raman spectroscopy as a process analytical technology tool for the understanding and the quantitative in-line monitoring of the homogenization process of a pharmaceutical suspension.

The aim of this study was to propose a Process Analytical Technology (PAT) strategy for the quantitative in-line monitoring of an aqueous pharmaceutical suspension using Raman spectroscopy. A screening design was used to study the significance of process variables (mixing speed and height of the stirrer in the reactor) and of formulation variables (concentration of the active pharmaceutical ingredient (API) ibuprofen and the viscosity enhancer (xanthan gum)) on the time required to homogenize an aqueous pharmaceutical model suspension as response variable. Ibuprofen concentration (10% and 15% (w/v)) and the height of stirrer (position 1 and 2) were discrete variables, whereas the viscosity enhancer (concentration range: 1-2 g L-1) and the mixing speed (700-1000 rpm) were continuous variables. Next, a multilevel full factorial design was applied to study the effect of the remaining significant variables upon the homogenization process and to establish the optimum conditions for the process. Interactions between these variables were investigated as well. During each design experiment, the conformity index (CI) method was used to monitor homogeneity of the suspension mixing system in real-time using Raman spectroscopy in combination with a fibre optical immersion probe. Finally, a principal component regression (PCR) model was developed and evaluated to perform quantitative real-time and in-line measurements of the API during the mixing process. The experimental design results showed that the suspension homogenization process is an irregular process, for which it is impossible to model the studied variables upon the measured response variable. However, applying the PCR model it is possible to predict in-line and real-time the concentration of the API in a suspension during a mixing process. In this study, it is shown that Raman spectroscopy is a suitable PAT tool for the control of the homogenization process of an aqueous suspension. Raman spectroscopy not only allowed real-time monitoring of the homogeneity of the suspension, but also helped (in combination with experimental design) to understand the process. Further, the technique allowed real-time and in-line quantification of the API during the mixing process.

Chemistry, Pharmaceutical↗

PubMed2004

In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy.

FT-Raman spectroscopy (in combination with a fibre optic probe) was evaluated as an in-line tool to monitor a blending process of diltiazem hydrochloride pellets and paraffinic wax beads. The mean square of differences (MSD) between two consecutive spectra was used to identify the time required to obtain a homogeneous mixture. A traditional end-sampling thief probe was used to collect samples, followed by HPLC analysis to verify the Raman data. Large variations were seen in the FT-Raman spectra logged during the initial minutes of the blending process using a binary mixture (ratio: 50/50, w/w) of diltiazem pellets and paraffinic wax beads (particle size: 800-1200 microm). The MSD-profiles showed that a homogeneous mixture was obtained after about 15 min blending. HPLC analysis confirmed these observations. The Raman data showed that the mixing kinetics depended on the particle size of the material and on the mixing speed. The results of this study proved that FT-Raman spectroscopy can be successfully implemented as an in-line monitoring tool for blending processes.

Fourier Analysis↗

PubMed2004

Development and validation of a direct, non-destructive quantitative method for medroxyprogesterone acetate in a pharmaceutical suspension using FT-Raman spectroscopy.

A simple linear regression method was developed and statistically validated for the direct and non-destructive quantitative analysis--without sample preparation--of the active pharmaceutical ingredient (API) medroxyprogesterone acetate (MPA) in an aqueous pharmaceutical suspension (150 mg in 1.0 ml) using FT-Raman spectroscopy. The linear regression was modelled by plotting the highest peak intensity of the vector normalized spectral band between 1630 and 1590 cm-1 against different MPA standard suspension concentrations. At this band, no spectral interferences from additives in the suspension are observed. The validated model was used for the quantification of a commercial suspension (150 mg in 1.0 ml) of the commercialized preparations. The same standards and samples were used, respectively, for the development and validation of a simple linear regression model and for the quantitative determination by means of HPLC-with sample preparation-as described for the related substances of MPA in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the claimed label concentration (150.01+/-0.96 mg/ml (n=6)). Applying the HPLC method, however, a systematic error was observed (157.77+/-0.94 mg/ml (n=6)). The direct FT-Raman method hence appears the most reliable for the quantification of the MPA component in suspension, compared to the HPLC method that requires sample preparation. The latter method provides a systematic error because the exact volume or density of a suspension sample is unknown. A precise isolation of fixed volumes from a suspension is rather unfeasible because of the continuous sagging of the suspended particles and their sticking to the used materials in the isolation process.

Chromatography, High Pressure Liquid↗

PubMed2003

Optimization and validation of a micellar electrokinetic chromatographic method for the analysis of several angiotensin-II-receptor antagonists.

We have optimized a micellar electrokinetic capillary chromatographic method for the separation of six angiotensin-II-receptor antagonists (ARA-IIs): candesartan, eprosartan mesylate, irbesartan, losartan potassium, telmisartan, and valsartan. A face-centred central composite design was applied to study the effect of the pH, the molarity of the running buffer, and the concentration of the micelle-forming agent on the separation properties. A combination of the studied parameters permitted the separation of the six ARA-IIs, which was best carried out using a 55-mM sodium phosphate buffer solution (pH 6.5) containing 15 mM of sodium dodecyl sulfate. The same system can also be applied for the quantitative determination of these compounds, but only for the more stable ARA-IIs (candesartan, eprosartan mesylate, losartan potassium, and valsartan). Some system parameters (linearity, precision, and accuracy) were validated.

Angiotensin II↗