Monitoring of high-load dose formulations based on co-processed and non co-processed excipients

This work presents the evaluation of a co-processed material for high-load dose formulations and its real-time monitoring by near-infrared (NIR) spectroscopy at the tablet press feed frame. The powder and tableting properties of co-processed material blends were evaluated and compared to the blend of the individual excipients. The formulations with the co-processed material showed excellent flow properties and were superior to the physical blend of individual excipients.

Highlights

Co-processed blends showed superior flow properties than non co-processed blends.

The effect of paddle wheel speed on tablets hardness was investigated.

The co-processed material NIR model presented significantly lower prediction errors.

Co-processed material reduces the sampling errors in the in-line measurements.

PAT tools can help in the pharmaceutical formulation development process.

Two NIR spectroscopic methods were developed to monitor ibuprofen concentration between 40.0 and 60.0% w/w, one method using a co-processed material as the main excipient and the other using the blend of the individual excipients. The NIR spectra were obtained while the powder blends flowed within a three-chamber feed frame from a Fette 3090 tablet press. The NIR spectroscopic method with the co-processed material presented better performance with significantly lower prediction error.

Variographic analysis demonstrated that using the co-processed material considerably reduces the sampling and analytical errors in the in-line determination of ibuprofen. The authors understand that this is the first study where the sampling errors are evaluated as a function of the excipients used in the pharmaceutical formulation. This study demonstrated that selecting a suitable excipient for the formulation helps optimize the manufacturing process, reducing the magnitude of the total measurement error.

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Materials: Ibuprofen powder (Ibuprofen 50, Ph.Eur./USP/JP/IP, BASF Corporation/Bishop, Texas, USA) was selected as a representative cohesive and agglomerated active pharmaceutical ingredient (API). Ludipress® (BASF AG, Ludwigshafen, Germany), crospovidone (Kollidon CL-F, BASF Corporation), povidone (Kollidon 30, BASF Corporation), and lactose monohydrate (Tablettose 70, Agglomerated, Ph.Eur., USP/NF, JP, Molkerei MEGGLE Wasserburg GMBH & Co.) were selected as excipients. Magnesium stearate (MgSt, N.F. non-Bovine, Tyco Healthcare/Mallinckrodt, St. Louis, Missouri, USA) was used as a lubricant in all powder blends.

Article information: Nobel O. Sierra-Vega, Krizia M. Karry, Rodolfo J. Romañach, Rafael Méndez, Monitoring of high-load dose formulations based on co-processed and non co-processed excipients, International Journal of Pharmaceutics, Volume 606, 2021. https://doi.org/10.1016/j.ijpharm.2021.120910.