Evaluation of the physical and mechanical properties of high drug load formulations: Wet granulation vs. novel foam granulation

Cantor, Stuart L.; Kothari, Suresh; Koo, Otilia M.

doi:10.1016/j.powtec.2009.05.003

Cited by 32 publications

(14 citation statements)

References 29 publications

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“…Tan et al 24 studied the method of foam granulation on a static powder bed and found it demonstrated a higher nucleating efficiency than drop (spray) addition due its lower soak-to-spread ratio. High-shear granulation trials 19,20,25,26 have evaluated the foam granulation approach in batch processes, finding further benefits related to a reduced amount of required binder solution, lower processing times, and greater consistency in binder addition without injector clogging. The present case study is the first opportunity to demonstrate the effectiveness of binder foaming technology as it is applied to a continuous process.…”

Section: Implementation Of Foam Granulation Extrusionmentioning

confidence: 99%

“…The binding surfactant in this case must demonstrate surface active foaming qualities in an aqueous environment, such as hydroxypropyl cellulose, hypromellose or other types of cellulose ethers, which are all noted foaming agents. Foam granulation has been successfully evaluated for high-shear batch mixers 19,20 , but this is the first study to consider its continuous application by twin screw extruder. This work compares direct liquid injection versus foam addition for wet granulation of excipients in a twin screw extruder based on the consistency of the produced granulated product.…”

Section: Introductionmentioning

confidence: 99%

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Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery

Thompson

Weatherley

Pukadyil

et al. 2011

Drug Development and Industrial Pharmacy

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This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of α-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules.

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Section: Implementation Of Foam Granulation Extrusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery

Thompson

Weatherley

Pukadyil

et al. 2011

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

show abstract

“…Porous particles can easily deform during compaction to create new bonding surfaces, thus affecting the tablet hardness [7]. Hardness of the tablet also depends on the granule surface area [8]. An appropriate design and operation of the granulation process can help to control the PSD and also help to achieve the desired flow characteristics of the particles.…”

Section: Introductionmentioning

confidence: 99%

A Multi-Scale Hybrid CFD-DEM-PBM Description of a Fluid-Bed Granulation Process

et al. 2014

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In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying the liquid binder on the fluidized powder bed. The fluid flow field has been solved implementing CFD principles and the behavior of the solid particles has been modeled using DEM techniques whereas the change in particle size has been quantified with the help of PBM. The liquid binder droplets have been modeled implicitly in DEM. A detailed understanding of the process aids in the development of better design, optimization and control strategies. The model predicts the evolution of important process variables (i.e., average particle diameter, particle size distribution (PSD) and particle liquid content) over time, which have qualitative similarity with experimentally observed trends. The advantage of incorporating the multi-scale approach is that the model can be used to study the distributions of collision frequencies, particle velocity and particle liquid content in different sections of the fluid bed granulator (FBG), in a more mechanistic manner.

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“…Sheskey et al 17,18 claimed that the foamed binders break quickly and dispersed uniformly within the powders, which effectively 6 distributed low levels of drug throughout the powder bed of the CR and IR tablet formulation during both high-shear and fluid-bed granulation. More recently, Cantor et al 19 evaluated the performance of conventional wet granulation and foam granulation in delivering high-drug load formulations which are brittle, viscoelastic, and ductile in characteristics. The authors 19 found that foam granulation significantly enhanced the plasticity of a granulation containing a brittle drug, but produced a material with mixer deformation behaviour for formulation containing a ductile drug.…”

Section: Foam Granulationmentioning

confidence: 99%

“…More recently, Cantor et al 19 evaluated the performance of conventional wet granulation and foam granulation in delivering high-drug load formulations which are brittle, viscoelastic, and ductile in characteristics. The authors 19 found that foam granulation significantly enhanced the plasticity of a granulation containing a brittle drug, but produced a material with mixer deformation behaviour for formulation containing a ductile drug. For viscoelastic materials, foam granulation did not enhance the plasticity of the formulation as well as conventional wet granulation process.…”

Section: Foam Granulationmentioning

confidence: 99%