Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

Chablani, Lipika; Taylor, Michael K.; Mehrotra, Amit; Rameas, Patrick; Stagner, William C.

doi:10.1208/s12249-011-9669-z

Cited by 72 publications

(34 citation statements)

References 13 publications

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“…Chablani et al [34] mounted an NIR probe in the granule-transfer module, which is situated just after the fluid-bed dryer, hence evaluating the dried granules. Two PLS models were constructed where the NIR spectra were regressed against the moisture content of the granules determined via Karl Fischer (KF) titration and "loss on drying", respectively.…”

Section: Twin-screw Granulationmentioning

confidence: 99%

Process Analytical Technology for continuous manufacturing of solid-dosage forms

Fonteyne

Vercruysse

Leersnyder

et al. 2015

TrAC Trends in Analytical Chemistry

145

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Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the advantages of continuous processing, so the critical quality attributes of continuously produced pharmaceuticals need to be monitored in real time. In 2004, the US Food and Drug Administration launched the process analytical technology (PAT) concept to stimulate the pharmaceutical industry to change from off-line to real-time quality testing. This review explores the implementation of PAT tools within continuous pharmaceutical processes (i.e., blending, spray drying, roller compaction, twin-screw granulation and compression), focusing on both opportunities and challenges.

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Section: Twin-screw Granulationmentioning

confidence: 99%

Process Analytical Technology for continuous manufacturing of solid-dosage forms

Fonteyne

Vercruysse

Leersnyder

et al. 2015

TrAC Trends in Analytical Chemistry

145

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“…Bakeev (7) has provided a recent compilation of PAT spectroscopic process analysis techniques. Our laboratory has reported the use of inline real-time near-infrared granule moisture content (8) and focused beam reflectance measurement particle size determination (9) for a commercial scale continuous granulation-drying-milling process. Previous studies have shown that LIF can be used in pharmaceutical blending to determine the blending end point (1,10).…”

Section: Introductionmentioning

confidence: 99%

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Shah

Stagner

2015

AAPS PharmSciTech

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Abstract. The effect of percent relative humidity (16-84% RH), moisture content (4.2-6.5% w/w MC), and compression force (4.9-44.1 kN CF) on the light-induced fluorescence (LIF) response of 10% w/w active pharmaceutical ingredient (API) compacts is reported. The fluorescent response was evaluated using two separate central composite designs of experiments. The effect of % RH and CF on the LIF signal was highly significant with an adjusted R 2 =0.9436 and p<0.0001. Percent relative humidity (p=0.0022), CF (p<0.0001), and % RH 2 (p=0.0237) were statistically significant factors affecting the LIF response. The effects of MC and CF on LIF response were also statistically significant with a p value <0.0001 and adjusted R 2 value of 0.9874. The LIF response was highly impacted by MC (p<0.0001), CF (p<0.0001), and MC 2 (p=0022). At 10% w/w API, increased % RH, MC, and CF led to a nonlinear decrease in LIF response. The derived quadratic model equations explained more than 94% of the data. Awareness of these effects on LIF response is critical when implementing LIF as a process analytical tool.KEY WORDS: design of experiments (DOE); fluorescence quenching; light-induced fluorescence (LIF); moisture; process analytical technology (PAT).

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“…: Schematic diagram of industrial granulation systems operated in a continuous production line [10].…”

mentioning

confidence: 99%

“…wetting and nucleation), some 7 empirical expressions are included in the model (leading to so-called semi-empirical or "grey box" models) 8 in order to allow simulation of the granulation system. 9 Although the underlying mechanisms of the granulation process are still being investigated, especially in 10 case of TSG where such detailed knowledge is not yet established [3], it is well motivated to model the 11 system at meso-or macro-scale such as to exploit the benefits of process system engineering (PSE) methods 12 and tools [16]. PSE tools rely on domain knowledge and mathematical and experimental techniques to build 13 computer models which relate the change at a molecular level to macro-scale system performance in order 14 to develop and optimise the system.…”

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confidence: 99%

See 1 more Smart Citation

Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production – A critical review

Kumar

Gernaey

Beer

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

109

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The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete continuous production line is still hampered by complex steps such as granulation and drying which are considered to be too inflexible to handle potential product change-overs. Granulation is necessary in order to achieve good flowability properties and better control of drug content uniformity. This paper reviews modelling and supporting measurement tools for the high shear wet granulation (HSWG) process, which is an important granulation technique due to the inherent benefits and the suitability of this unit operation for the desired switch to continuous mode. For gaining improved insight of the complete system, particle-level mechanisms are required to be better understood, and linked with an appropriate meso-or macro-scale model. A brief review has been provided to understand the mechanisms of the granulation process at micro or particle-level such as those involving wetting and nucleation, aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro-to meso-scale, are discussed. The DEM approach has a major role to play in future research as it bridges the gap between micro-and meso-scales. Furthermore, interesting developments in the measurement technologies are discussed with a focus towards inline measurements of the granulation process to obtain experimental data which are required for developing good models. Based on the current state of the developments, the review focuses on the twin screw granulator as a device for * Email address: ingmar.nopens@ugent.be, Tel.: +32 (0)9 264 61 96; fax: +32 (0) continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open research questions are identified. These questions need to be answered in the future in order to fill the knowledge gap that currently exists both at micro-and macro-scale, and which is currently limiting the further development of the process to its full potential in pharmaceutical applications.

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Inline Real-Time Near-Infrared Granule Moisture Measurements of a Continuous Granulation–Drying–Milling Process

Cited by 72 publications

References 13 publications

Process Analytical Technology for continuous manufacturing of solid-dosage forms

Process Analytical Technology for continuous manufacturing of solid-dosage forms

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production – A critical review

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