Effect of process parameters and formulation properties on the lead-lag between in-line NIR tablet press feed frame and off-line NIR tablet measurements.

The use of in-line near-infrared (NIR) measurements for tablet potency monitoring and diversion was studied. First, the optimal sample size for in-line NIR measurements inside the feed chute and the dosing and filling chamber of the tablet press feed frame was determined to allow proper comparison between these different measurement positions. Because of the considerably longer measurement time needed to obtain the same sample size inside the feed chute compared to the feed frame, the possibility of powder segregation inside the feed chute and the additional powder mixing inside the feed frame, the latter is preferred over the feed chute for in-line blend potency monitoring.

A hybrid model for multipoint real time potency observation in continuous direct compression manufacturing operations.

The ongoing transition from batch to continuous manufacturing offers both challenges and opportunities in the field of oral solid dosage form production. In turn, Process Analytical Technology (PAT) offers a path towards the successful deployment of continuous tablet manufacturing in rotary tablet presses. One promising PAT tool for this endeavour is the NIR-derived potency measurement.

Determination and understanding of lead-lag between in-line NIR tablet press feed frame and off-line NIR tablet measurements.

The influence of different tableting process parameters on lead-lag was studied by collecting in-line near-infrared (NIR) spectra in the filling chamber of the tablet press feed frame and off-line NIR tablet data. Lead-lag is defined as the difference in time and API concentration between the measured in-line feed frame NIR response and the off-line NIR tablet data. Lead-lag results from the product formulation blend undergoing additional mixing after passing the NIR probe inside the feed frame, before being filled into the dies of the tablet press.

Development of a tablet press feed frame lead lag determination model using in-line and off-line NIR measurements.

For continuous pharmaceutical manufacturing of oral solid dosages, it is essential that product quality is measured inline. In this application, a continuous rotary tablet press is used. The goal is a model-based assessment of the quality of the blend in the feed frame to determine whether the concentration of the active pharmaceutical ingredient (API) will be within the prescribed limits.

Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form.

A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to develop a calibration set. The calibration set was designed to create compositional and raw material lots variation using minimum resources.

Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press.

A calibration model for in-line API quantification based on near infrared (NIR) spectra collection during tableting in the tablet press feed frame was developed and validated. First, the measurement set-up was optimised and the effect of filling degree of the feed frame on the NIR spectra was investigated. Secondly, a predictive API quantification model was developed and validated by calculating the accuracy profile based on the analysis results of validation experiments.

Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press.

Context: The negative impact of magnesium stearate (MgSt) on the hardness of tablets is a well-known phenomenon, but the influence of paddle movement in the forced feeder on the lubricant effect during tablet compression is often neglected.

Objective: The purpose of this research was to investigate the influence of paddle speed in the forced feeder on tablet tensile strength (TS).

Materials And Methods: Mixtures of microcrystalline cellulose (MCC) and MgSt (0.

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.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework.

Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press.

Context: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.

Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets.

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.