The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration

23 Jul 2024 | Contributor(s): Movilla-Meza, Nathaly A., Sierra-Vega, Nobel O., Alvarado-Hernández, Bárbara B., Méndez, Rafael, Romañach, Rodolfo J.

Purpose: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Methods: Calibration models...

Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients

23 Jul 2024 | Contributor(s): Patel, Dhavalkumar S, Méndez, Rafael, Romañach, Rodolfo J

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning...

The Use of Near-Infrared and Microwave Resonance Sensing to Monitor a Continuous Roller Compaction Process

09 Jun 2023 | Contributor(s): Austin, John, Gupta, Anshu, Mcdonnell, Ryan, Reklaitis, Gintaras V., Harris, Michael T

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity...

Supervisory Control System for Monitoring a Pharmaceutical Hot Melt Extrusion Process

09 Jun 2023 | Contributor(s): Markl, Daniel, Wahl, Patrick R, Menezes, José C, Koller, Daniel M, Kavsek, Barbara, Francois, Kjell, Roblegg, Evaa, Khinast, Johannes G.

Continuous pharmaceutical manufacturing processes are of increased industrial interest and require uni- and multivariate Process Analytical Technology (PAT) data from different unit operations to be aligned and explored within the Quality by Design (QbD) context. Real-time pharmaceutical process...

Robustness of a continuous direct compression line against disturbances in feeding

09 Jun 2023 | Contributor(s): Karttunen A.-P., Poms J., Sacher S., Sparén A., Ruiz Samblás C., Fransson M., Martin De Juan L., Remmelgas J., Wikström H., Hsiao W.-K., Folestad S., Korhonen O.

The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances. These disturbances mimicked typical variations that can be encountered during long-term...

Real-time monitoring of drug concentration in a continuous powder mixing process using NIR spectroscopy

09 Jun 2023 | Contributor(s): Vanarase, Aditya, Alcalà, Manel, Jerez-Rozo, Jackeline, Muzzio, Fernando, Romañach, Rodolfo

A non-destructive NIR spectroscopic method was used to acquire on-line spectra of a continuous mixing process, and evaluate the performance of this novel system. Partial least squares (PLS) calibration models were developed and used for real-time determination of active ingredient concentration...

Real-time process monitoring in a semi-continuous fluid-bed dryer - microwave resonance technology versus near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Peters, Johanna, Teske, Andreas, Taute, Wolfgang, Döscher, Claas, Höft, Michael, Knöchel, Reinhard, Breitkreutz, Jörg

The trend towards continuous manufacturing in the pharmaceutical industry is associated with an increasing demand for advanced control strategies. It is a mandatory requirement to obtain reliable real-time information on critical quality attributes (CQA) during every process step as the decision...

Real-Time Quantification of Low-Dose Cohesive Formulations within a Sampling Interface for Flowing Powders

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel. O., Romañach, Rodolfo J., Mendez, Rafael

This study investigates the performance of a sampling interface for monitoring cohesive, flowing powder formulations with Hausner's Ratio and Carr's Index higher than 1.5 and 35%, respectively. The sampler device was operated in combination with near-infrared (NIR) spectroscopy to quantify...

Real-time monitoring of particle size distribution in a continuous granulation and drying process by near infrared spectroscopy

09 Jun 2023 | Contributor(s): Pauli, V, Roggo, YKleinebudde, P, Krumme, M

In continuous granulation, it can be important to control granules particle size distribution (PSD), as it may affect final product quality. Near infrared spectroscopy (NIRS) is already a routine analytical procedure within pharmaceutical continuous manufacturing for the in-line analysis of...

Quality-by-Design III: Application of Near-Infrared Spectroscopy to Monitor Roller Compaction In-process and Product Quality Attributes of Immediate Release Tablets

09 Jun 2023 | Contributor(s): Kona, Ravikanth, Fahmy, Raafat M., Claycamp, Gregg, Polli, James E., Martinez, Marilyn, Hoag, Stephen W.

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller...

Process analytical technology for continuous manufacturing tableting processing: A case study

09 Jun 2023 | Contributor(s): Pauli, Victoria, Pellegatti, Laurent, Nguyen Trung, Nhat Quang, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Roggo, Yves, Krumme, Markus

The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...

Process analytical technology in continuous manufacturing of a commercial pharmaceutical product

09 Jun 2023 | Contributor(s): Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...

On-line monitoring of blend uniformity in continuous drug product manufacturing process -The impact of powder flow rate and the choice of spectrometer: Dispersive vs. FT

09 Jun 2023 | Contributor(s): Shi, Zhenqi, McGhehey, Kathryn C, Leavesley, Ian M., Manley, Leo F.

One of the commonly acknowledged issues in continuous manufacturing of drug products is how to provide a representative sampling on flowing powder to assure its blend uniformity. An investigation was conducted to improve understanding on the impact of powder flow rate under different continuous...

Opportunities for Process Control and Quality Assurance Using Online NIR Analysis to a Continuous Wet Granulation Tableting Line

09 Jun 2023 | Contributor(s): Palmer J., O’Malley C.J., Wade M.J., Martin E.B., Page T., Montague G.A.

This paper investigates the application of online near-infrared measurements as a means to measure blend uniformity in a continuous tableting line. Underlying all the monitoring and control methods is the ability to measure key tablet properties online at a rate suitable for control purposes. The...

Near Infrared Method Development for a Continuous Manufacturing Blending Process

09 Jun 2023 | Contributor(s): Colon, Yleana, Florian, Miguel, Acevedo, David, Mendez, Rafael, Romañach, Rodolfo

Purpose This study describes the validation of a near infrared spectroscopic method for monitoring a continuous manufacturing system. The achievement of this goal requires determining the near infrared (NIR) method’s accuracy, precision, obtaining an estimate of the sample volume analyzed, and...

Near-infrared spectroscopic applications in pharmaceutical particle technology

09 Jun 2023 | Contributor(s): Razuc, M, Grafia, AGallo, L, Ramirez-Rigo, MV, Romanach, RJ

Near-infrared spectroscopy (NIRS) is nowadays an established analytical technique in the pharmaceutical industry. The aim of this review is to present the progress of NIRS in providing useful information for pharmaceutical particle technology. NIR methods are now developed to characterize a wide...

Near-infrared Spectroscopy for the In-line Characterization of Powder Voiding Part I: Development of the Methodology

09 Jun 2023 | Contributor(s): Ropero, Jorge, Beach, Lauren, Alcala, Manel, Rentas, Raizza, Dave, Rajesh N., Romanach, Rodolfo J.

In-line near-infrared spectroscopy (NIR) spectra were acquired and analyzed to assess the relationship between physical and chemical properties of voiding powders and their spectral changes. NIR spectra were obtained for powders voiding from a conical glass funnel while the powder flow was...

Near-Infrared Spectroscopy for the In-Line Characterization of Powder Voiding Part II: Quantification of Enhanced Flow Properties of Surface Modified Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Beach, Lauren, Ropero, Jorge, Mujumdar, Ajit, Alcala, Manel, Romanach, Rodolfo J., Dave, Rajesh N.

In this work, dry-particle coating was used to modify the surface properties of active pharmaceutical ingredients (APIs) having extremely poor flow properties. Near-infrared (NIR) spectroscopy was utilized as a novel approach to characterize the improved flow behavior of APIs and their blends....

Nondestructive measurements of the compact strength and the particle-size distribution after milling of roller compacted powders by near-infrared spectroscopy

09 Jun 2023 | Contributor(s): Gupta, A, Peck, GE, Miller, RW, Morris, KR

Compact strength and the particle-size distribution of milled roller compacted compacts were correlated to the slope of the best-fit line through near-infrared spectra for samples prepared under different roll speeds and feed rates. The above correlations were found to hold for compacts prepared...

In-line monitoring of low drug concentration of flowing powders in a new sampler device

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel O, Méndez, Rafael, Martínez-Cartagena, Pedro; Alvarado-Hernández, Bárbara B; Romañach, Rodolfo J.

A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of...

In-line monitoring of the drug content of powder mixtures and tablets by near-infrared spectroscopy during the continuous direct compression tableting process

09 Jun 2023 | Contributor(s): Järvinen, Kristiina, Hoehe, Wolfgang, Järvinen, Maiju, Poutiainen, Sami, Juuti, Mikko, Borchert, Sven

Continuous manufacturing methods offer economic and quality advantages when compared with batch manufacturing methods. In continuous manufacturing, one requires real time assurance of quality of product via the implementation of PAT tools. This study focuses on an in-line near-infrared (NIR)...

In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy

09 Jun 2023 | Contributor(s): Sierra-Vega, Nobel, Sánchez-Paternina, Adriluz, Maldonado, Nadja, Cárdenas, Vanessa, Romañach, Rodolfo, Mendez, Rafael

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed...

How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain

09 Jun 2023 | Contributor(s): Wahl, P. R., Peter, A., Wolfgang, M., Khinast, J. G.

Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a...

Fit-for-Purpose Miniature NIR Spectroscopy for Solid Dosage Continuous Manufacturing

09 Jun 2023 | Contributor(s): Karry, Krizia, Singh, Ravendra, Muzzio, Fernando

Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo

Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....