Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

Portier, Christoph; Vígh, Tamás; Pretoro, G. Di; Beer, Thomas De; Vervaet, Chris

doi:10.1016/j.ijpharm.2020.119068

Cited by 17 publications

(17 citation statements)

References 42 publications

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“…It was stated that the main factor that affects the particle size distribution (PSD) is the liquid-to-solid (L/S) ratio. At low L/S ratio, the PSD exhibited bimodality, whereas at high L/S ratio the PSD showed unimodal behavior, those findings were in agreement with other works [ 8 , 10 ]. From that experimental data, a one-dimensional population balance model was developed for predicting the PSD at the outlet of the granulator starting from the pre-blend using aggregation and breakage as the main phenomena that take place in the granulation process [ 11 ].…”

Section: Introductionsupporting

confidence: 93%

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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Section: Introductionsupporting

confidence: 93%

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

et al. 2021

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“…Generally, the ratio of the water soluble filler to MCC is above 1 to avoid excessive water addition required by MCC. Due to the continuous nature of the subsequent drying process, residence time and drying capacity are limited, restricting the amount of water that can be evaporated [ 59 ].…”

Section: Influence Of Raw Materials Propertiesmentioning

confidence: 99%

“…Considering continuous twin screw granulation, initial studies mainly focused on the effect of process settings [ 49 , 50 , 51 ] and screw configurations [ 52 , 53 , 54 ]. However, more recent studies have highlighted the importance of formulation and raw material properties [ 2 , 12 , 27 , 46 , 47 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] and aspects related to drug product registration such as PAT implementation and control strategies [ 7 , 10 , 62 ]. Since most of the studies on twin screw wet granulation focus on a single formulation, often not containing an active pharmaceutical ingredient (API), results are difficult to generalize.…”

Section: Introductionmentioning

confidence: 99%

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

Portier

Vervaet

2021

Pharmaceutics

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Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in batch mode such as high shear granulation and fluid bed granulation, several equipment manufacturers have designed their own manufacturing setup. This has led to a steep increase in the research output in this field. However, most studies still focused on a single (often placebo) formulation, hence making it difficult to assess the general validity of the obtained results. Therefore, current review provides an overview of recent progress in the field of continuous twin screw wet granulation, with special focus on the importance of the formulation aspect and raw material properties. It gives practical guidance for novel and more experienced users of this technique and highlights some of the unmet needs that require further research.

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“…This was attributed to more material dissolving in the granulation liquid, forming more solid bonds upon recrystallization of mannitol during drying [16,30]. A friability threshold of 30% was used to define the granule quality, as above this limit, granules were susceptible to breakage and attrition during downstream operations [11,16,24,26,[35][36][37]. As a binder was considered more efficient when a lower amount of liquid was required to meet the 30% friability limit, the required L/S-ratio to meet this limit was used to distinguish binders on effectiveness.…”

Section: Binder Characterization Technique Abbreviation Characterizatmentioning

confidence: 99%

“…However, only a single type of binder (hydroxypropyl cellulose (HPC)) was used to confirm these observations [21]. Other studies have assessed the binder types' effect (e.g., hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), HPC, native and pregelatinized starches, maltodextrins, and vinylpyrrolidone-vinyl acetate copolymer) on granule quality for TSG [9,10,17,20,[22][23][24][25][26][27][28][29]. Nevertheless, the use of different formulations is hindering the comparison on binder efficiency between different studies, as the other components also contributed to the binding performance, affecting the granulation process [30].…”

Section: Introductionmentioning

confidence: 99%

Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

et al. 2021

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The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

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Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

Cited by 17 publications

References 42 publications

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

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

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

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