Recent trends and future perspective of pharmaceutical wet granulation for better process understanding and product development

Thapa, P.; Tripathi, Julu; Jeong, Seong Hoon

doi:10.1016/j.powtec.2018.12.080

Cited by 66 publications

(18 citation statements)

References 177 publications

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“…As stated in [35], binders of viscosity less than a critical value will be referred to as "lower viscosity" binders and binders of viscosity larger than this critical value will be referred to as "higher viscosity" binders. With "lower viscosity" binders, the degree of size enlargement increases with increasing binder viscosity because the granule growth occurs by layering and, conversely, the extent of size enlargement decreases with increasing viscosity with "higher viscosity" binders because the growth occurs by coalescence [35,57]. Secondly, APS increases as the primary particle size increases when keeping operating variables and other material attributes constant, which agrees with the conclusions in [20,22].…”

Section: Computational Experiments On Model Verification For Sfbgsupporting

confidence: 77%

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

et al. 2019

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The pharmaceutical tablet manufacturing process (PTMP) via wet granulation holds a critical position in pharmaceutical industry. The interest in integrating mechanistic process modeling into the pharmaceutical development has been increased because simulation model is a prerequisite for process design, analysis, control, and optimization. So the simulation modeling for PTMP via wet granulation is very necessary and significant. This study aims at proposing a simulation modeling framework for PTMP via spray fluidized bed granulation (SFBG), which is one of the most widely used wet granulation techniques in pharmaceutical industry. For SFBG, a simulation model that simultaneously involves the influences of operating variables and material attributes on average particle size (APS) is firstly developed, and then a drying model to determine the particle moisture content is introduced to be coupled with the established model predicting APS. For PTMP, considering the important effect of porosity on tablet qualities, a model describing the changes in tablet porosity is developed based on a promoted form of the Heckel equation, and then several recognized models that are all related to porosity are introduced or constructed to calculate important tablet quality indexes. The feasibility and effectiveness of the developed simulation models are validated by performing a computational experimental study to explore the scientific understanding of process and process quality control.

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Section: Computational Experiments On Model Verification For Sfbgsupporting

confidence: 77%

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

et al. 2019

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“…In this context, the twin-screw wet granulation has become a promising wet granulation technique in the pharmaceutical industry for continuous manufacturing of solid dosage forms due to advantages such as design flexibility, short residence time and throughput range [ 1 ]. Various works conducted on twin-screw wet granulation have investigated the aspects of the process or the equipment design that determine the quality attributes of the produced granules [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. In contrast, less investigations have been approached to delve into the physical mechanisms that govern the process and are necessary to predict it.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the multiple published models to simulate the twin-screw wet granulation process [ 1 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 ], a complete or more generic model that involves material properties, process parameters and perhaps screw configurations, is to the author’s best knowledge not available in literature [ 6 ]. This work seeks to take the first steps to address the development of a generic model, which from an industrial perspective is desirable to reduce the number of experiments required and therefore expedite the time to market for new products.…”

Section: Introductionmentioning

confidence: 99%

Improvement of a 1D Population Balance Model for Twin-Screw Wet Granulation by Using Identifiability Analysis

et al. 2021

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Recently, the pharmaceutical industry has undergone changes in the production of solid oral dosages from traditional inefficient and expensive batch production to continuous manufacturing. The latest advancements include increased use of continuous twin-screw wet granulation and application of advanced modeling tools such as Population Balance Models (PBMs). However, improved understanding of the physical process within the granulator and improvement of current population balance models are necessary for the continuous production process to be successful in practice. In this study, an existing compartmental one-dimensional PBM of a twin-screw granulation process was improved by altering the original aggregation kernel in the wetting zone as a result of an identifiability analysis. In addition, a strategy was successfully applied to reduce the number of model parameters to be calibrated in both the wetting zone and kneading zones. It was found that the new aggregation kernel in the wetting zone is capable of reproducing the particle size distribution that is experimentally observed at different process conditions as well as different types of formulations, varying in hydrophilicity and API concentration. Finally, it was observed that model parameters could be linked not only to the material properties but also to the liquid to solid ratio, paving the way to create a generic PBM to predict the particle size distribution of a new formulation.

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“…Polymorphism widely exists in active pharmaceutical ingredients (APIs), and it may occur during the formulation or manufacturing processes. Wet granulation is the most commonly used process in the pharmaceutical industry for achieving agglomeration of the primary powder particles into a workable granule with a solvent or liquid binder [1]. The main objective of the process is to improve the material properties, such as improved flowability and compression, improved uniform drug distribution and content uniformity, reduced dustiness and minimized segregation [2,3].…”

Section: Introductionmentioning

confidence: 99%

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

Zhao

et al. 2021

Pharmaceutics

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The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

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Recent trends and future perspective of pharmaceutical wet granulation for better process understanding and product development

Cited by 66 publications

References 177 publications

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

Simulation Modeling of a Pharmaceutical Tablet Manufacturing Process via Wet Granulation

Improvement of a 1D Population Balance Model for Twin-Screw Wet Granulation by Using Identifiability Analysis

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

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