Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models.

Classically, the end point detection during fluid bed drying has been performed using indirect parameters, such as the product temperature or the humidity of the outlet drying air. This paper aims at comparing those classic methods to both in-line moisture and solid-state determination by means of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study.

Real-time assessment of critical quality attributes of a continuous granulation process.

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production.

Rapid solid-state analysis of freeze-dried protein formulations using NIR and Raman spectroscopies.

Noninvasive near-infrared (NIR) and Raman spectroscopies were applied to provide a fast and efficient insight into the formation of different mannitol solid forms occurring in freeze-dried formulations. Multivariate data analysis clearly showed the formation of δ-mannitol in the presence of protein, whereas β-mannitol was observed in the absence of protein.The multivariate analysis of the NIR spectra also gave an indication for the formation of mannitol hemihydrate in the absence of protein.

Towards a robust water content determination of freeze-dried samples by near-infrared spectroscopy.

The possibility for determination of the water content in pharmaceutical samples by near-infrared (NIR) spectroscopy has been more widely investigated in the past few years. However, many studies claim that changes in sample composition will require the establishment of a new method. The aim of this study was several fold: firstly to investigate validation aspects of water content determination in samples with varying composition and furthermore to see if a model based solely on freeze-dried mannitol-sucrose mixtures can be established that will be able to predict water contents for samples containing proteins, excipients or having a lower density of freeze-dried solids.