Cette invention se rapporte a une composition pharmaceutique solide, a liberation prolongee, pour... more Cette invention se rapporte a une composition pharmaceutique solide, a liberation prolongee, pour administration orale, adaptee a une posologie quotidienne reduite, dont l'ingredient therapeutique est un medicament de base faiblement soluble. Ladite formulation comporte un melange d'un alginate soluble dans l'eau, d'un sel complexe de l'acide alginique et d'un acide carboxylique organique avec le medicament therapeutique. Une realisation particuliere de cette invention concerne une forme posologique a administrer une fois par jour, dont l'ingredient therapeutique est constitue de clarithromycine.
Although miniaturisation of vibrational spectrometers began approximately a decade ago, only with... more Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (<100 g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can...
Pharmaceutical packaging is the coordinated system that encloses and protects a dosage form. Coun... more Pharmaceutical packaging is the coordinated system that encloses and protects a dosage form. Counterfeit drugs have caused deaths, and lead to the failure of public trust in the healthcare system and the pharmaceutical manufacturers. The authentication of packaging materials requires a trained forensic approach. Advanced instrumentation has become expensive, for example with hyper- and multi-spectral techniques, and multivariate data interpretation can be non-standard. There is always a need for rapid screening of suspect materials, particularly across market surveys where rapid, non-destructive determination counterfeits is required to segregate and allow further downstream forensic analysis. The development of Fourier transfer infra-red (FT-IR) spectroscopy in the 1970's facilitated the rapid data capture and analysis of solids and liquids. Since then thousands of spectra are commercially available for identification purposes based on transmission and, more recently, attenuate...
Transmission near-infrared (NIR) spectroscopy was used for the rapid and non-destructive determin... more Transmission near-infrared (NIR) spectroscopy was used for the rapid and non-destructive determination of the content of a hormone steroid in single intact tablets. Tablets produced for clinical trial purposes containing 5, 10, 15, 20 and 30 mg (2.94, 5.88, 8.82, 11.76 and 17.64% m/m, respectively) were used to develop calibration models without the need to specially prepare any out of specification tablets. Reference values for the individual tablets used in the NIR calibration models and test set were measured by reversed-phase high performance liquid chromatography (HPLC). Partial least squares regression using standard normal variate transformed second-derivative spectra over the range 800 to 1040 nm gave the optimum calibration model with a standard error of calibration of 0.52 mg per tablet. Measurements of an independent test set gave comparable results (standard error of prediction 0.31 mg per tablet). Measurement errors for a single tablet (RSD < 2.5% for a given active ...
A novel optimisation algorithm is presented for full spectrum calibration models in near-infrared... more A novel optimisation algorithm is presented for full spectrum calibration models in near-infrared (NIR) spectroscopy. The algorithm is used to investigate the affect of removing continuous spectral regions on parameters critical to the validity of the model (e.g. explained variance, bias etc.) and ultimately identify and remove problem areas of the spectrum. As an example of its application, this paper shows how to optimise partial least squares regression (PLSR) calibration models for predicting moisture content within an intact pharmaceutical product and how problems due to changes in the nature of samples since setting up the original model may be eliminated. On application of two validated calibration models to a new set of samples unacceptable results were obtained for bias (20.26 and 20.21% m/m moisture content) between the NIR predicted values and the true values (Karl Fischer analysis). The optimisation algorithm identified small regions of the spectrum, which if included in development of the models contributed significant bias to the final prediction. On removal of these problem regions the calibration models were found to be equally accurate and precise, but with the added advantage of robustness to a variable region of the sample spectrum (bias reduced to 20.05 and 20.09% m/m). † Electronic supplementary information (ESI) available: Figures of the effects of removing spectral windows on partial least squares regression. See http://www.rsc.org/suppdata/an/b3/b309233j/ This journal is
A procedure was developed for different modes of calibration transfer in near-infrared (NIR) spec... more A procedure was developed for different modes of calibration transfer in near-infrared (NIR) spectroscopy, which included a method for the selection of a subset of samples appropriate for transfer. As a worked example, these guidelines were applied to the transfer of a multivariate calibration model, representing a validated NIR single tablet assay for the active within an intact pharmaceutical product, between three equivalent dispersive NIR transmission instruments. Transfer was first evaluated between two instruments, representing the situation where both were available during calibration development. A spectral correction method alone, applied to the transfer instrument, was not sufficient to facilitate transfer, with further optimisation of the calibration model using a novel wavelength selection algorithm necessary to remove regions of the spectral range that resulted in skewed predictions on the second instrument. Through this approach, a single calibration model was found to be equally accurate and precise on the two instruments. A procedure, using the Kennard-Stone algorithm, is described for determining a reduced number of samples as a transfer set using only the spectral information from the original instrument. The purpose of the subset was to permit transfer to a new instrument where that instrument was not available until after calibration development or where it was undesirable to re-measure the full sample set (i.e. due to excessive reference chemistry). Utilising the transfer set, transfer to a third instrument was evaluated. The calibration model, optimised between the first two instruments, was not directly applicable for the third instrument, with further wavelength selection required to remove a small region of spectral data. On completion, using a full statistical evaluation, a single calibration model was found to be equally accurate and precise on all three instruments.
Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (3... more Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (34-49% v/v), propylene glycol (20-35% v/v) and water (11-20% m/m) contents within a multi-component pharmaceutical oral liquid by measurement directly through the amber plastic bottle packaging. Spectra were collected in the range 7302-12 000 cm 21 and calibration models set-up using partial least-squares regression (PLSR) and multiple linear regression. Reference values for the three components were measured using capillary gas chromatography (ethanol and propylene glycol) and Karl Fischer (water) assay procedures. The calibration and test sets consisted of production as well as laboratory batches that were made to extend the concentration ranges beyond the natural production variation. The PLSR models developed gave standard errors of prediction (SEP) of 1.1% v/v for ethanol, 0.9% v/v for propylene glycol and 0.3% m/m for water. For each component the calibration model was validated in terms of: linearity, repeatability, intermediate precision and robustness. All the methods produced statistically favourable outcomes. Ten production batches independent of the calibration and test sets were also challenged against the PLSR models, giving SEP values of 1.3% v/v (ethanol), 1.0% v/v (propylene glycol) and 0.2% m/m (water). NIR transmission spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 min.
Journal of Pharmaceutical and Biomedical Analysis, 2003
A rapid near-infrared spectrometric (NIR) method was qualified for use with the quantitative anal... more A rapid near-infrared spectrometric (NIR) method was qualified for use with the quantitative analysis of selamectin and moisture in topical formulations. Selamectin is currently marketed as a pet endectocide and is available in several formulations for cats and dogs. The use of NIR in this investigation replaces the in-process testing by liquid chromatography and concurrently provided moisture content that would otherwise only be available with additional Karl Fischer titration investigations. A seven-factor partial least square regression (PLS) of the second derivative spectra encompassing the wavelength region of 1450 Á/2200 nm was used to quantify both selamectin and moisture content. A second three-factor PLS solely for water content was also applied and compared with the full model. This qualification confirms that this method may be used to quantitate selamectin and moisture as a process tool or to examine finished good samples. Each sample can be rapidly analyzed within 5 min on the current bench top system. #
The following commentary was developed by the National Marrow Donor Program Cord Blood Advisory G... more The following commentary was developed by the National Marrow Donor Program Cord Blood Advisory Group and is intended to provide an overview of umbilical cord blood (UCB) processing, summarize the current state of potency assays used to characterize UCB, and defi ne limitations of the assays and future needs of the cord blood banking and transplant community. The UCB banking industry is eager to participate in the development of standardized assays to uniformly characterize cellular therapy products that are manufactured in a variety of ways. This paper describes the desired qualities of these assays and how the industry proposes to co-operate with developers to bring relevant assays to market. To that end, the National Marrow Donor Program (NMDP) Cord Blood Bank Network is available to serve as a resource for UCB testing material, research and development consulting, and product/assay testing in an accredited UCB manufacturing environment.
a new methodology to perform multivariate product quality monitoring based on the net analyte sig... more a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is separated from the remaining systematic variation due to all other compounds in the matrix. This enhances the ability to flag products out of statistical control. Using control charts, the analyte content, variation of other compounds, and residual variation can be monitored. As an example, NAS-SQC is used to appreciate the control content uniformity of a commercially available pharmaceutical tablet product measured with nearinfrared spectroscopy. Using the NAS chart, the active pharmaceutical ingredient (API) content is easily monitored for new tablets. However, since quality is a multivariate property, other quality parameters of the tablets are also monitored simultaneously. It will be demonstrated that, besides the API content, the water content of the tablets as well as the homogeneity of the other compounds is monitored.
ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, ... more ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (&lt;100g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can be achieved. In this respect, the present communication has put to test the performance of this micro-NIR system with reference to selected qualitative and quantitative pharmaceutical applications.
Cette invention se rapporte a une composition pharmaceutique solide, a liberation prolongee, pour... more Cette invention se rapporte a une composition pharmaceutique solide, a liberation prolongee, pour administration orale, adaptee a une posologie quotidienne reduite, dont l'ingredient therapeutique est un medicament de base faiblement soluble. Ladite formulation comporte un melange d'un alginate soluble dans l'eau, d'un sel complexe de l'acide alginique et d'un acide carboxylique organique avec le medicament therapeutique. Une realisation particuliere de cette invention concerne une forme posologique a administrer une fois par jour, dont l'ingredient therapeutique est constitue de clarithromycine.
Although miniaturisation of vibrational spectrometers began approximately a decade ago, only with... more Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (<100 g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can...
Pharmaceutical packaging is the coordinated system that encloses and protects a dosage form. Coun... more Pharmaceutical packaging is the coordinated system that encloses and protects a dosage form. Counterfeit drugs have caused deaths, and lead to the failure of public trust in the healthcare system and the pharmaceutical manufacturers. The authentication of packaging materials requires a trained forensic approach. Advanced instrumentation has become expensive, for example with hyper- and multi-spectral techniques, and multivariate data interpretation can be non-standard. There is always a need for rapid screening of suspect materials, particularly across market surveys where rapid, non-destructive determination counterfeits is required to segregate and allow further downstream forensic analysis. The development of Fourier transfer infra-red (FT-IR) spectroscopy in the 1970's facilitated the rapid data capture and analysis of solids and liquids. Since then thousands of spectra are commercially available for identification purposes based on transmission and, more recently, attenuate...
Transmission near-infrared (NIR) spectroscopy was used for the rapid and non-destructive determin... more Transmission near-infrared (NIR) spectroscopy was used for the rapid and non-destructive determination of the content of a hormone steroid in single intact tablets. Tablets produced for clinical trial purposes containing 5, 10, 15, 20 and 30 mg (2.94, 5.88, 8.82, 11.76 and 17.64% m/m, respectively) were used to develop calibration models without the need to specially prepare any out of specification tablets. Reference values for the individual tablets used in the NIR calibration models and test set were measured by reversed-phase high performance liquid chromatography (HPLC). Partial least squares regression using standard normal variate transformed second-derivative spectra over the range 800 to 1040 nm gave the optimum calibration model with a standard error of calibration of 0.52 mg per tablet. Measurements of an independent test set gave comparable results (standard error of prediction 0.31 mg per tablet). Measurement errors for a single tablet (RSD < 2.5% for a given active ...
A novel optimisation algorithm is presented for full spectrum calibration models in near-infrared... more A novel optimisation algorithm is presented for full spectrum calibration models in near-infrared (NIR) spectroscopy. The algorithm is used to investigate the affect of removing continuous spectral regions on parameters critical to the validity of the model (e.g. explained variance, bias etc.) and ultimately identify and remove problem areas of the spectrum. As an example of its application, this paper shows how to optimise partial least squares regression (PLSR) calibration models for predicting moisture content within an intact pharmaceutical product and how problems due to changes in the nature of samples since setting up the original model may be eliminated. On application of two validated calibration models to a new set of samples unacceptable results were obtained for bias (20.26 and 20.21% m/m moisture content) between the NIR predicted values and the true values (Karl Fischer analysis). The optimisation algorithm identified small regions of the spectrum, which if included in development of the models contributed significant bias to the final prediction. On removal of these problem regions the calibration models were found to be equally accurate and precise, but with the added advantage of robustness to a variable region of the sample spectrum (bias reduced to 20.05 and 20.09% m/m). † Electronic supplementary information (ESI) available: Figures of the effects of removing spectral windows on partial least squares regression. See http://www.rsc.org/suppdata/an/b3/b309233j/ This journal is
A procedure was developed for different modes of calibration transfer in near-infrared (NIR) spec... more A procedure was developed for different modes of calibration transfer in near-infrared (NIR) spectroscopy, which included a method for the selection of a subset of samples appropriate for transfer. As a worked example, these guidelines were applied to the transfer of a multivariate calibration model, representing a validated NIR single tablet assay for the active within an intact pharmaceutical product, between three equivalent dispersive NIR transmission instruments. Transfer was first evaluated between two instruments, representing the situation where both were available during calibration development. A spectral correction method alone, applied to the transfer instrument, was not sufficient to facilitate transfer, with further optimisation of the calibration model using a novel wavelength selection algorithm necessary to remove regions of the spectral range that resulted in skewed predictions on the second instrument. Through this approach, a single calibration model was found to be equally accurate and precise on the two instruments. A procedure, using the Kennard-Stone algorithm, is described for determining a reduced number of samples as a transfer set using only the spectral information from the original instrument. The purpose of the subset was to permit transfer to a new instrument where that instrument was not available until after calibration development or where it was undesirable to re-measure the full sample set (i.e. due to excessive reference chemistry). Utilising the transfer set, transfer to a third instrument was evaluated. The calibration model, optimised between the first two instruments, was not directly applicable for the third instrument, with further wavelength selection required to remove a small region of spectral data. On completion, using a full statistical evaluation, a single calibration model was found to be equally accurate and precise on all three instruments.
Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (3... more Fourier transform near-infrared (FT-NIR) spectroscopy was used to quantify rapidly the ethanol (34-49% v/v), propylene glycol (20-35% v/v) and water (11-20% m/m) contents within a multi-component pharmaceutical oral liquid by measurement directly through the amber plastic bottle packaging. Spectra were collected in the range 7302-12 000 cm 21 and calibration models set-up using partial least-squares regression (PLSR) and multiple linear regression. Reference values for the three components were measured using capillary gas chromatography (ethanol and propylene glycol) and Karl Fischer (water) assay procedures. The calibration and test sets consisted of production as well as laboratory batches that were made to extend the concentration ranges beyond the natural production variation. The PLSR models developed gave standard errors of prediction (SEP) of 1.1% v/v for ethanol, 0.9% v/v for propylene glycol and 0.3% m/m for water. For each component the calibration model was validated in terms of: linearity, repeatability, intermediate precision and robustness. All the methods produced statistically favourable outcomes. Ten production batches independent of the calibration and test sets were also challenged against the PLSR models, giving SEP values of 1.3% v/v (ethanol), 1.0% v/v (propylene glycol) and 0.2% m/m (water). NIR transmission spectroscopy allowed all three liquid constituents to be non-invasively measured in under 1 min.
Journal of Pharmaceutical and Biomedical Analysis, 2003
A rapid near-infrared spectrometric (NIR) method was qualified for use with the quantitative anal... more A rapid near-infrared spectrometric (NIR) method was qualified for use with the quantitative analysis of selamectin and moisture in topical formulations. Selamectin is currently marketed as a pet endectocide and is available in several formulations for cats and dogs. The use of NIR in this investigation replaces the in-process testing by liquid chromatography and concurrently provided moisture content that would otherwise only be available with additional Karl Fischer titration investigations. A seven-factor partial least square regression (PLS) of the second derivative spectra encompassing the wavelength region of 1450 Á/2200 nm was used to quantify both selamectin and moisture content. A second three-factor PLS solely for water content was also applied and compared with the full model. This qualification confirms that this method may be used to quantitate selamectin and moisture as a process tool or to examine finished good samples. Each sample can be rapidly analyzed within 5 min on the current bench top system. #
The following commentary was developed by the National Marrow Donor Program Cord Blood Advisory G... more The following commentary was developed by the National Marrow Donor Program Cord Blood Advisory Group and is intended to provide an overview of umbilical cord blood (UCB) processing, summarize the current state of potency assays used to characterize UCB, and defi ne limitations of the assays and future needs of the cord blood banking and transplant community. The UCB banking industry is eager to participate in the development of standardized assays to uniformly characterize cellular therapy products that are manufactured in a variety of ways. This paper describes the desired qualities of these assays and how the industry proposes to co-operate with developers to bring relevant assays to market. To that end, the National Marrow Donor Program (NMDP) Cord Blood Bank Network is available to serve as a resource for UCB testing material, research and development consulting, and product/assay testing in an accredited UCB manufacturing environment.
a new methodology to perform multivariate product quality monitoring based on the net analyte sig... more a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is separated from the remaining systematic variation due to all other compounds in the matrix. This enhances the ability to flag products out of statistical control. Using control charts, the analyte content, variation of other compounds, and residual variation can be monitored. As an example, NAS-SQC is used to appreciate the control content uniformity of a commercially available pharmaceutical tablet product measured with nearinfrared spectroscopy. Using the NAS chart, the active pharmaceutical ingredient (API) content is easily monitored for new tablets. However, since quality is a multivariate property, other quality parameters of the tablets are also monitored simultaneously. It will be demonstrated that, besides the API content, the water content of the tablets as well as the homogeneity of the other compounds is monitored.
ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, ... more ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (&lt;100g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can be achieved. In this respect, the present communication has put to test the performance of this micro-NIR system with reference to selected qualitative and quantitative pharmaceutical applications.
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Papers by Neville Broad