The quality by design (QbD) initiative is promoting a better understanding of excipient performan... more The quality by design (QbD) initiative is promoting a better understanding of excipient performance and the identification of critical material attributes (CMAs). Despite microcrystalline cellulose (MCC) being one of the most popular direct compression binders, only a few studies attempted identifying its CMAs. These studies were based either on a limited number of samples or on MCC produced on a small scale and/or in conditions that deviate from those normally encountered in production. The present work utilizes multivariate analyses first to describe a large database of MCCs produced on a commercial scale, including an overview of their physicochemical properties, and secondly to correlate the most significant material attributes with tabletability. Particle size and moisture content are often considered as the most common if not the sole CMAs with regard to MCC performance in direct compression. The evaluation of more than 80 neat MCCs and the performance of selected samples in a model formulation revealed the importance of other potential critical attributes such as tapped density. Drug product developers and excipient suppliers should work together to identify these CMAs, which may not always be captured by the certificate of analysis.
International journal of pharmaceutics, Jan 18, 2015
The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (... more The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (Gattefossé, France) in order to improve the oral bioavailability of the drug. Particles from gas saturated solutions (PGSS) process was chosen for investigation as a manufacturing process for producing a solid dispersion. The PGSS process was optimized according to the in vitro drug dissolution profile obtained using a biphasic dissolution test. Using a design of experiments approach, the effects of nine experimental parameters were investigated using a PGSS apparatus provided by Separex(®) (Champigneulles, France). Within the chosen experimental conditions, the screening results showed that the drug loading level, the autoclave temperature and pressure, the connection temperature and the nozzle diameter had a significant influence on the dissolution profile of fenofibrate. During the optimization step, the three most relevant parameters were optimized using a central composite design, w...
Journal of Pharmaceutical and Biomedical Analysis, 2014
Towards a real time release approach for manufacturing tablets using NIR spectroscopy, Journal of... more Towards a real time release approach for manufacturing tablets using NIR spectroscopy, Journal of Pharmaceutical and Biomedical Analysis (2014), http://dx.
The quality by design (QbD) initiative is promoting a better understanding of excipient performan... more The quality by design (QbD) initiative is promoting a better understanding of excipient performance and the identification of critical material attributes (CMAs). Despite microcrystalline cellulose (MCC) being one of the most popular direct compression binders, only a few studies attempted identifying its CMAs. These studies were based either on a limited number of samples or on MCC produced on a small scale and/or in conditions that deviate from those normally encountered in production. The present work utilizes multivariate analyses first to describe a large database of MCCs produced on a commercial scale, including an overview of their physicochemical properties, and secondly to correlate the most significant material attributes with tabletability. Particle size and moisture content are often considered as the most common if not the sole CMAs with regard to MCC performance in direct compression. The evaluation of more than 80 neat MCCs and the performance of selected samples in a model formulation revealed the importance of other potential critical attributes such as tapped density. Drug product developers and excipient suppliers should work together to identify these CMAs, which may not always be captured by the certificate of analysis.
International journal of pharmaceutics, Jan 18, 2015
The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (... more The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (Gattefossé, France) in order to improve the oral bioavailability of the drug. Particles from gas saturated solutions (PGSS) process was chosen for investigation as a manufacturing process for producing a solid dispersion. The PGSS process was optimized according to the in vitro drug dissolution profile obtained using a biphasic dissolution test. Using a design of experiments approach, the effects of nine experimental parameters were investigated using a PGSS apparatus provided by Separex(®) (Champigneulles, France). Within the chosen experimental conditions, the screening results showed that the drug loading level, the autoclave temperature and pressure, the connection temperature and the nozzle diameter had a significant influence on the dissolution profile of fenofibrate. During the optimization step, the three most relevant parameters were optimized using a central composite design, w...
Journal of Pharmaceutical and Biomedical Analysis, 2014
Towards a real time release approach for manufacturing tablets using NIR spectroscopy, Journal of... more Towards a real time release approach for manufacturing tablets using NIR spectroscopy, Journal of Pharmaceutical and Biomedical Analysis (2014), http://dx.
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Papers by Fabrice Krier