Wet Granulation Processes

Hapgood, Karen; Litster, James D.

doi:10.1002/9780470882221.ch39

Cited by 3 publications

(3 citation statements)

References 85 publications

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“…In drug product formulation wet granulation is an important unit operation and is an example of particle design in which generating larger granules is the desired outcome. 9 Specifically, wet granulation incorporates API in combination with excipients and binders to produce granules with desirable mechanical properties. By understanding the mechanism of wet granulation from drug formulation science, we should be able to better understand and ultimately control or prevent agglomeration from occurring in our drying processes within API manufacturing.…”

Section: Introductionmentioning

confidence: 99%

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Development and Application of Laboratory Tools To Predict Particle Properties upon Scale-Up in Agitated Filter-Dryers

Ende

Birch

Brenek

et al. 2013

Org. Process Res. Dev.

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Agitated filter-dryers (AFDs) are commonly used for performing both filtration and drying operations in the manufacture of active pharmaceutical ingredients (APIs) and intermediates. Successful scale-up from the laboratory to manufacturing AFD equipment requires that physical properties specifications such as particle size be consistently met in addition to chemical purity specifications. Depending on the API–solvent system and equipment operational parameters, undesired attrition or agglomeration may occur, so an improved understanding of these phenomena upon scale-up is of key importance. In this paper, we describe recent advances in laboratory methods, based on material characterization methods common to drug product formulation development, to better assess the risk of agglomeration and attrition potential upon scale-up. These methods provide data to evaluate solid behavior, in both wet and dry states, associated with processing in an AFD. For agglomeration prediction, the application of mixer torque rheometry for measuring the propensity to form granules or agglomerates of API wet cake is described as well as how to categorize agglomeration risk based on the output of this testing. For measuring attrition propensity, the application of powder rheometry is described, and risk categories are proposed. For both testing methods, good agreement was seen between laboratory predictions and actual behavior upon scale-up. For compounds evaluated as high risk for attrition or agglomeration, alternate drying protocols are recommended to mitigate risk. In addition, progress on enhancing cycle times for difficult to dry materials is discussed.

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Section: Introductionmentioning

confidence: 99%

“…In drug product formulation wet granulation is an important unit operation and is an example of particle design in which generating larger granules is the desired outcome . Specifically, wet granulation incorporates API in combination with excipients and binders to produce granules with desirable mechanical properties.…”

Section: Introductionmentioning

confidence: 99%

Development and Application of Laboratory Tools To Predict Particle Properties upon Scale-Up in Agitated Filter-Dryers

Ende

Birch

Brenek

et al. 2013

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…In practice, the operating ranges, or the control space, of these process variables are determined based on historical or experimental data. Adjustments of the process variables during out of control situations are still mainly guided by the know‐how of the operator 8,137. However, the rate‐dependent connection between the process variables and granule quality is intricate, which results in significant batch‐to‐batch variation despite the best use of univariate control systems 138,139.…”

Section: Granulationmentioning

confidence: 99%

Towards Better Process Understanding: Chemometrics and Multivariate Measurements in Manufacturing of Solid Dosage Forms

Matero

Berg

Poutiainen

et al. 2013

Journal of Pharmaceutical Sciences

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A quality by design approach to scale-up of high-shear wet granulation process

Pandey

Badawy

2015

Drug Development and Industrial Pharmacy

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High-shear wet granulation is a complex process that in turn makes scale-up a challenging task. Scale-up of high-shear wet granulation process has been studied extensively in the past with various different methodologies being proposed in the literature. This review article discusses existing scale-up principles and categorizes the various approaches into two main scale-up strategies - parameter-based and attribute-based. With the advent of quality by design (QbD) principle in drug product development process, an increased emphasis toward the latter approach may be needed to ensure product robustness. In practice, a combination of both scale-up strategies is often utilized. In a QbD paradigm, there is also a need for an increased fundamental and mechanistic understanding of the process. This can be achieved either by increased experimentation that comes at higher costs, or by using modeling techniques, that are also discussed as part of this review.

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Wet Granulation Processes

Cited by 3 publications

References 85 publications

Development and Application of Laboratory Tools To Predict Particle Properties upon Scale-Up in Agitated Filter-Dryers

Development and Application of Laboratory Tools To Predict Particle Properties upon Scale-Up in Agitated Filter-Dryers

Towards Better Process Understanding: Chemometrics and Multivariate Measurements in Manufacturing of Solid Dosage Forms

A quality by design approach to scale-up of high-shear wet granulation process

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