A Bayesian Approach to Kinetic Modeling of Accelerated Stability Studies and Shelf Life Determination.

Kinetic modeling of accelerated stability data serves an important purpose in the development of pharmaceutical products, providing support for shelf life claims and expediting the path to clinical implementation. In this context, a Bayesian kinetic modeling framework is considered, accommodating different types of nonlinear kinetics with temperature and humidity dependent rates of degradation and accounting for the humidity conditions within the packaging to predict the shelf life. In comparison to kinetic modeling based on nonlinear least-squares regression, the Bayesian approach allows for interpretable posterior inference, flexible error modeling and the opportunity to include prior information based on historical data or expert knowledge.

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.

Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG.

NIR spectroscopic method for the in-line moisture assessment during drying in a six-segmented fluid bed dryer of a continuous tablet production line: Validation of quantifying abilities and uncertainty assessment.

This study focuses on the thorough validation of an in-line NIR based moisture quantification method in the six-segmented fluid bed dryer of a continuous from-powder-to-tablet manufacturing line (ConsiGma™ 25, GEA Pharma Systems nv, Wommelgem, Belgium). The moisture assessment ability of an FT-NIR spectrometer (Matrix™-F Duplex, Bruker Optics Ltd, UK) equipped with a fiber-optic Lighthouse Probe™ (LHP, GEA Pharma Systems nv, Wommelgem, Belgium) was investigated. Although NIR spectroscopy is a widely used technique for in-process moisture determination, a minority of NIR spectroscopy methods is thoroughly validated.

Particle sizing measurements in pharmaceutical applications: comparison of in-process methods versus off-line methods.

It has been previously described that when a sample's particle size is determined using different sizing techniques, the results can differ considerably. The purpose of this study was to review several in-process techniques for particle size determination (Spatial Filtering Velocimetry, Focused Beam Reflectance Measurements, Photometric Stereo Imaging, and the Eyecon® technology) and compare them to well-known and widespread off-line reference methods (laser diffraction and sieve analysis). To start with, a theoretical explanation of the working mechanism behind each sizing technique is presented, and a comparison between them is established.

Development of a fluid bed granulation process control strategy based on real-time process and product measurements.

This article describes the results of three case studies conducted consecutively, in order to develop a process control strategy for a top-spray fluid bed granulation process. The use of several real-time particle size (i.e.

Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: A review.

Fluidized bed granulation is a widely applied wet granulation technique in the pharmaceutical industry to produce solid dosage forms. The process involves the spraying of a binder liquid onto fluidizing powder particles. As a result, the (wetted) particles collide with each other and form larger permanent aggregates (granules).

Prediction of quality attributes of continuously produced granules using complementary pat tools.

Manufacturers of pharmaceutical solid dosage forms aim for a reduced production time and a shorter "time-to-market." Therefore, continuous manufacturing gains increasing interest in the pharmaceutical industry. For continuous manufacturing, the quality of produced pharmaceuticals should be assessed in real-time (in-line, on-line, and at-line) and not via the traditional off-line, often destructive and time-consuming analysis methods that supply the desired information only hours after sampling.

Real-time image-based investigation of spheronization and drying phenomena using different pellet formulations.

Extrusion-spheronization (ES) is a frequently used agglomeration process in the pharmaceutical industry to manufacture spherical solid units or pellets with a narrow size and shape distribution. In this study, photometric stereo imaging was applied in real-time during the final steps of the ES process, being spheronization and drying. In addition to the pellet size distribution of undispersed (wet) samples, the imaging technique captures visual information on pellet shape and surface brightness.

Batch statistical process control of a fluid bed granulation process using in-line spatial filter velocimetry and product temperature measurements.

Fluid bed granulation is a batch process, which is characterized by the processing of raw materials for a predefined period of time, consisting of a fixed spraying phase and a subsequent drying period. The present study shows the multivariate statistical modeling and control of a fluid bed granulation process based on in-line particle size distribution (PSD) measurements (using spatial filter velocimetry) combined with continuous product temperature registration using a partial least squares (PLS) approach. Via the continuous in-line monitoring of the PSD and product temperature during granulation of various reference batches, a statistical batch model was developed allowing the real-time evaluation and acceptance or rejection of future batches.

Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes.

Within the Process Analytical Technology (PAT) framework, it is of utmost importance to obtain critical process and formulation information during pharmaceutical processing. Process analyzers are the essential PAT tools for real-time process monitoring and control as they supply the data from which relevant process and product information and conclusions are to be extracted. Since the last decade, near infrared (NIR) and Raman spectroscopy have been increasingly used for real-time measurements of critical process and product attributes, as these techniques allow rapid and nondestructive measurements without sample preparations.

Evaluation of in-line spatial filter velocimetry as PAT monitoring tool for particle growth during fluid bed granulation.

In this study, the feasibility of spatial filter velocimetry (SFV) as process analytical technology tool for the in-line monitoring of the particle size distribution during top spray fluidized bed granulation was examined. The influence of several process (inlet air temperature during spraying and drying) and formulation variables (HPMC and Tween 20 concentration) upon the particle size distribution during processing, and the end product particle size distribution, tapped density and Hausner ratio was examined using a design of experiments (DOE) (2-level full factorial design, 19 experiments). The trend in end granule particle size distributions of all DOE batches measured with in-line SFV was similar to the off-line laser diffraction (LD) data.

Importance of using complementary process analyzers for the process monitoring, analysis, and understanding of freeze drying.

The aim of the present paper is to demonstrate the importance of using complementary process analyzers (PAT tools) for the process monitoring, analysis, and understanding of freeze drying. A mannitol solution was used as a model system. Raman spectroscopic, near-infrared (NIR) spectroscopic, plasma emission spectroscopic, and wireless temperature measurements (TEMPRIS) were simultaneously performed in-line and real-time during each freeze-drying experiment.

In-line and real-time process monitoring of a freeze drying process using Raman and NIR spectroscopy as complementary process analytical technology (PAT) tools.

The aim of the present study was to examine the complementary properties of Raman and near infrared (NIR) spectroscopy as PAT tools for the fast, noninvasive, nondestructive and in-line process monitoring of a freeze drying process. Therefore, Raman and NIR probes were built in the freeze dryer chamber, allowing simultaneous process monitoring. A 5% (w/v) mannitol solution was used as model for freeze drying.

Raman spectroscopy as a process analytical technology (PAT) tool for the in-line monitoring and understanding of a powder blending process.

The aim of this study is to propose a strategy to implement a PAT system in the blending step of pharmaceutical production processes. It was examined whether Raman spectroscopy can be used as PAT tool for the in-line and real-time endpoint monitoring and understanding of a powder blending process. A screening design was used to identify and understand the significant effects of two process variables (blending speed and loading of the blender) and of a formulation variable (concentration of active pharmaceutical ingredient (API): diltiazem hydrochloride) upon the required blending time (response variable).