Sampling Devices for In-line near Infrared Spectroscopy Monitoring of Powder Blend Homogeneity in Continuous Manufacturing

 
The use of process analytical technology (PAT) in the pharmaceutical industry has significantly increased as an effect of regulatory guidelines and the transition towards continuous manufacturing of oral solid dosage forms. In the direct compression process, the most common way to assess the homogeneity of powder blends is after the final mixing operation, followed by end-point testing of tablets. However, focusing on the homogeneity of powder blends does not consider the potential of segregation during material storage and powder transport and also faces severe sampling issues.
In this study, NIR spectroscopy was used to study powder blend homogeneity at two positions in the continuous manufacturing process; after the first blender and in the tablet press feed-frame. The focus of the study was on sample presentation at the two positions, and several sampling devices were tested, in order to improve the quality of the NIR measurements. These were made in laboratory settings that simulated in-line measurements in a vertical tube between the two blenders and in the feed frame of the tablet press. A model formulation consisting of powder mixtures of a drug substance, mannitol, microcrystalline cellulose (MCC), croscarmellose sodium (NaCMC) and sodium stearyl fumarate (NaSF) was used for the experiments. A design of experiments, where the API was varied at five levels while MCC, NaCMC and NaSF were varied at two levels, was used for the calibration powder blends.
Orthogonal partial least squares (OPLS) calibration models for the NIR measurements in the two positions were developed and validated with independent test sets. The results for the sampling devices tested are compared and the future implementation in the continuous manufacturing equipment is discussed
Presented by Anders Sparén, Associate Principal Scientist at AstraZeneca

Anders Sparén has an MSc in chemical engineering and a PhD in analytical chemistry, both from the Royal Institute of Technology in Stockholm, Sweden. He joined AstraZeneca in 1995 and has mainly been working with analytical method development, vibrational spectroscopy, the design of experiments, multivariate analysis and process analytical technology. Today he holds a role as an associate principal scientist in chemical/formulation characterisation with vibrational spectroscopy, which includes the responsibility for developing and implementing rapid, non-destructive analytical methods in drug development projects and manufacturing, as well as applying them to material characterisation and process analytical technology.
Anders has experience both from R&D and manufacturing & supply and has an extensive network of collaborators within and outside AstraZeneca, as well as an active science career with 40 published papers, including three patents in the field of life science. His academic partners over the years have included the Royal Institute of Technology in Stockholm and Lund University, and the research has been focused on near-infrared spectroscopy and transmission Raman spectroscopy. Today, he is active in a collaboration on THz spectroscopy with Chalmers University of Technology in Gothenburg, Sweden.
Followed Powder Blend Homogeneity Monitoring with the Viavi MicroNIR PAT-W
The MicroNIR PAT-W wireless NIR spectrometer  is used in monitoring blend uniformity in pharmaceutical manufacturing. The PAT-W is a rugged, IP65/67 rated instrument with no moving parts. The PAT-W, with >8 hours battery life, WiFi communication and onboard gravity sensor is well suited for use on tumble blenders in regulated facilities. Viavi’s Linear Variable Filter technology, optical fiber-free design and dual onboard tungsten lamps ensure excellent stability, long lifetime and minimal instrument-to-instrument variability. Viavi MicroNIR Pro software provides data acquisition and chemometric model building, and assures compliance with Title 21 CFR Part 11, USP chapter 1119 and EP chapter 2.2.40. OPC communication and control are also available for use in process environments.
Presented by Ed Gooding, MicroNIR Photonic Applications Specialist at VIAVI Solutions

Ed Gooding is an expert in optical spectroscopy and a chemometrics enthusiast. His PhD thesis work at the University of Pennsylvania involved ultrafast dynamics of small molecules in solution. As a postdoctoral associate at the University of Pittsburgh he built a nanosecond temperature jump apparatus to monitor peptide and protein folding via time-resolved UV resonance Raman spectroscopy. He continued research into peptide folding dynamics via CD and FTIR at Swarthmore College. Ed was Spectroscopy Product Line Manager at Princeton Instruments and later worked at a hyperspectral imaging startup. He joined Viavi Solutions in 2018 as a Field Applications Engineer.
Sponsored by Viavi Solutions

VIAVI Solutions designs and manufactures the MicroNIR™ family of Near Infrared (NIR) spectrometer sensor instruments for non-destructive analysis in both handheld and on-line applications in food, agriculture, pharmaceutical, chemical, and R&D. The process analytical models – MicroNIR PAT-U and MicroNIR PAT-W – are versatile process spectrometers designed for use in real-time monitoring (batch or continuous) of manufacturing operations. The MicroNIR PAT-U is a compact, lightweight, rugged, USB-powered spectrometer sensor in a sapphire-and-stainless steel case, designed for monitoring processes in fixed equipment.  MicroNIR PAT-W is a lightweight, wireless spectrometer sensor designed for monitoring processes in moving equipment like tumble blenders.  Both models will soon be available for hazardous (Ex) locations.  The MicroNIR OnSite-W is a rugged, wireless, handheld analyzer for rapid analysis of raw materials and critical quality attributes of finished product.  All MicroNIR instruments employ proprietary VIAVI Linear Variable Filter (LVF) technology, which eliminates free-space optics and associated calibration variations and also eliminates preventive maintenance.  MicroNIR instruments are supported by a wide array of sampling and measurement accessories and MicroNIR Pro software, a complete chemometric modeling package that incorporates functions for monitoring blend uniformity and also interoperates with industry-standard modeling packages.