Desire L Massart | PubMed Health

PubMed2004

Evaluating "fast" micellar monolithic liquid chromatography for high-throughput quantitative structure-retention relationship screening.

The recently introduced monolithic silica columns were tested for their use in micellar liquid chromatography. Micellar methods are utilized in high-throughput quantitative structure-retention relationships to estimate an indicator of the membrane permeability of drugs, namely, the octanol-water partition coefficient, log P. The monolithic column's ability to function at higher flow rates might be useful to speed up these chromatographic methods estimating the log P. Therefore, the elution behavior of diverse basic pharmaceutical substances was determined on a classical particle-based and a monolithic column, both with and without a micellar medium in the mobile phase. Utilizing among others principal component analysis, the extent to which these methods differ in retention characteristics was examined in the context of high-throughput determination of log P. Results indicate that combining monolithic columns with micellar media leads to faster log P and possibly even better permeability predictions.

Journal Article↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗