scholarly journals Understanding the Effect of Granulation and Milling Process Parameters on the Quality Attributes of Milled Granules

Processes ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 683
Author(s):  
Lalith Kotamarthy ◽  
Nirupaplava Metta ◽  
Rohit Ramachandran
Keyword(s):  
Particle Size ◽  
Bulk Density ◽  
Quality Attributes ◽  
Milling Process ◽  
Oral Dosage ◽  
Impeller Speed ◽  
Unit Operation ◽  
Particle Size Reduction ◽  
The Impact ◽  
Milled Product

Milling is an essential unit operation used for particle size reduction in solid oral dosage manufacturing. The breakage of particles in a comil is due to the intense shear applied on the particles between impeller and the screen. Breakage also occurs due to the impact from a rotating impeller. Particles exit the mill based on their size relative to the aperture size of the screen bores. This study was set up to understand the working of the comil better. A new CPP (Critical Process Parameter), in the form of batch loading was identified. It was found that there are two different regimes (quasi static regime and impact regime) in which a comil generally operates, and the effect of the CPP’s (batch loading and impeller speed) on these regimes was studied. Knowledge of the effect of upstream operations on a particular unit operation is of significant importance, especially for pharmaceutical industry. For this reason, the effect of granulation variables such as liquid-to-solid ratio, granulator impeller speed and the amount of binder in the formulation were analyzed. Milled particle size distribution and other critical quality attributes such as bulk density, friability, and porosity were studied. Batch loading and the interaction effect of batch loading with impeller speed are significant parameters that affect the quality attributes of the mill. Predictive regression models were developed for throughput of the mill, milled product bulk density and milled product tapped density (with an R2 of 0.987, 0.953, 0.995 respectively) to enable their use in downstream process modeling.

Effects of particle size on the quality attributes of wheat flour made by the milling process

2019 ◽  
Vol 97 (2) ◽  
pp. 172-182 ◽  
Author(s):  
Sen Ma ◽  
Chongchong Wang ◽  
Li Li ◽  
Xiaoxi Wang
Keyword(s):  
Particle Size ◽  
Wheat Flour ◽  
Quality Attributes ◽  
Milling Process

scholarly journals Implementing Feedback Granule Size Control in a Continuous Dry Granulation Line Using Controlled Impeller Speed of the Granulation Unit, Compaction Force and Gap Width

2020 ◽  
Author(s):  
Annika Wilms ◽  
Andreas Teske ◽  
Robin Meier ◽  
Raphael Wiedey ◽  
Peter Kleinebudde
Keyword(s):  
Particle Size ◽  
Process Parameters ◽  
Control Strategies ◽  
Granule Size ◽  
Oral Dosage ◽  
Impeller Speed ◽  
Median Particle Size ◽  
Dry Granulation ◽  
Median Particle ◽  
Roll Compaction

Abstract Purpose In continuous manufacturing of pharmaceuticals, dry granulation is of interest because of its large throughput capacity and energy efficiency. In order to manufacture solid oral dosage forms continuously, valid control strategies for critical quality attributes should be established. To this date, there are no published control strategies for granule size distribution in continuous dry granulation. Methods In-line laser diffraction was used to determine the size of granules in a continuous roll compaction/dry granulation line (QbCon® dry). Different process parameters were evaluated regarding their influences on granule size. The identified critical process parameters were then incorporated into control strategies. The uncontrolled and the controlled processes were compared based on the resulting granule size. In both processes, a process parameter was changed to induce a shift in median particle size and the controller had to counteract this shift. Results In principle, all process parameters that affect the median particle size could also be used to control the particle size in a dry granulation process. The sieve impeller speed was found to be well suited to control the median particle size as it reacts fast and can be controlled independently of the throughput or material. Conclusion The median particle size in continuous roll compaction can be controlled by adjusting process parameters depending on real-time granule size measurements. The method has to be validated and explored further to identify critical requirements to the material and environmental conditions.

Particle Size Reduction of Biomaterials Using Cryogenic Milling Process

2005 ◽  
Vol 475-479 ◽  
pp. 2403-2406 ◽  
Author(s):  
Sang Mok Lee ◽  
Hoon Jae Park ◽  
Seung Soo Kim ◽  
Tae Hoon Choi ◽  
E.Z. Kim ◽  
...  
Keyword(s):  
Particle Size ◽  
Ball Milling ◽  
Xrd Analysis ◽  
Milling Process ◽  
Degree Of Crystallinity ◽  
Particle Size Reduction ◽  
Cryogenic Milling ◽  
Ball Milling Process ◽  
Before And After ◽  
The Degree Of Crystallinity

Reducing the particle size of drug materials down to submicron is an important matter in pharmaceutical industry. Cryogenic milling technology is one of the mechanical milling processes, which is mostly utilized in refining grain size of metal and ceramics at extremely low temperature environment. This technique has not been readily studied in application to medical and biotechnology. This paper, therefore, describes the application of cryogenic milling process to reduce particle size of Ibuprofen. The shape and size of the Ibuprofen particle before and after the cryogenic ball milling process were analyzed. XRD analysis was performed to examine a change in crystallinity of Ibuprofen by the cryogenic ball milling process. The results showed that the size of Ibuprofen particles was reduced to 1/10 or less of its initial size. The results also showed that the degree of crystallinity of Ibuprofen was slightly reduced after cryogenic ball milling with nitrogen.

scholarly journals New Aspects of MgH2 Morphological and Structural Changes during High-Energy Ball Milling

Materials ◽  
2020 ◽  
Vol 13 (20) ◽  
pp. 4550
Author(s):  
Tomasz Czujko ◽  
Ewelina E. Oleszek ◽  
Mariusz Szot
Keyword(s):  
Activation Energy ◽  
Particle Size ◽  
Powder Particle ◽  
Structural Changes ◽  
High Energy ◽  
Decomposition Temperature ◽  
Milling Process ◽  
Size Analysis ◽  
Crystallographic Structure ◽  
Particle Size Reduction

Magnesium hydride, despite the decomposition temperature being incompatible with the operating temperature of a typical PEM cell, is still considered a prospective material for hydrogen storage. Hence, this paper presents new aspects of the influence of milling time on the structural changes and temperature of MgH2 decomposition, with particular emphasis on the changes taking place in the first few seconds of the milling process. This paper presents qualitative and quantitative changes in the powder particle morphology determined using scanning electron microscopy (SEM) and infrared particle size analysis (IPS) systems. The crystallographic structure of the powders in the initial state and after mechanical milling was characterized by X-ray diffraction. The decomposition temperature and activation energy were determined by the differential scanning calorimetry (DSC). Changes in the activation energy and decomposition temperature were observed after only 1–2 min of the milling process. Two basic stages of the milling process were distinguished that impacted the MgH2 decomposition temperature, i.e., mechanical activation and a nanostructuring process. The activation was associated with the initial stage of particle size reduction and an increase in the fraction of fresh chemically active powder particle surfaces. On the other hand, the nanostructuring process was related to an additional decrease in the MgH2 decomposition temperature.

scholarly journals Experimental and CFD investigation of the mixing of MMA emulsion polymerization in a stirred tank reactor

2021 ◽  
Author(s):  
Shideh F. Roudsari
Keyword(s):  
Molecular Weight ◽  
Particle Size ◽  
Emulsion Polymerization ◽  
Particle Number ◽  
Polymerization Reaction ◽  
Impeller Speed ◽  
Glass Temperature ◽  
Agitation Rate ◽  
Number Density ◽  
The Impact

Although significant advances have been achieved in emulsion polymerization in recent decades, the effect of mixing on this type of polymerization has not been fully delineated yet. In fact, mixing plays a significant role in the performance of an emulsion polymerization reaction. For instance, in case of a very low agitation rate, larger droplets are generated and phase separation, which limits the diffusion mechanism, may occur. In contrast, vigorous agitation can result in reduced nucleation of particles. Therefore, the main objective of this study is to investigate the impact of mixing parameters (e.g. impeller speed, impeller type, impeller number, and baffles) on the monomer conversion, the polymer average molecular weight, particle size and size distributions, transition glass temperature, and number of particles. To achieve this objective, the emulsion polymerization of methyl methacrylate (MMA) was carried out in a lab-scale reactor equipped with a top-entry agitator, 4 wall baffles, a U shaped cooling coil, and a temperature controller. To analyze the reactive flow inside the polymerization reactor, a novel computational fluid dynamics (CFD) model was developed. The multiple reference frames (MRF) technique, k-ε model, and mixture model approach were employed to model the impeller rotation, turbulence, and multiphase flow, respectively. The particle number density distribution within the reactor was also estimated by means of the population balance approach, which employs a discrete method to describe the nucleation and growth of the polymer particles. The experimental data and CFD results showed that the installation of the baffles enhanced the particle size and molecular weight but reduced the conversion and particle number. The number density achieved using the Rushton impeller was higher than that for the pitched blade impeller. The results revealed that the effect of the impeller speed on the characteristics of the polymer attained using the pitched-blade turbine was more prominent than that for the Rushton turbine. It was also found that the impact of the impeller speed on the polymer characteristics was much more pronounced for the double pitched-blade turbines rather than for the double Rushton turbines.

Particle Size Reduction of Biomaterials Using Cryogenic Milling Process

2005 ◽  
pp. 2403-2406
Author(s):  
Sang Mok Lee ◽  
Hoon Jae Park ◽  
Seung Soo Kim ◽  
Tae Hoon Choi ◽  
E.Z. Kim ◽  
...  
Keyword(s):  
Particle Size ◽  
Milling Process ◽  
Size Reduction ◽  
Particle Size Reduction ◽  
Cryogenic Milling

scholarly journals Structure and Magnetic Properties Of Fe/Si Nanoparticles Prepared by High Energy Milling Process

2021 ◽  
Vol 11 (2) ◽  
pp. 239
Author(s):  
Muhammad Rifai ◽  
Yunasfi Yunasfi ◽  
Engkir Sukirman ◽  
Yosef Sarwanto ◽  
Mujamilah Mujamilah
Keyword(s):  
Phase Transition ◽  
Particle Size ◽  
Magnetic Properties ◽  
Iron Oxides ◽  
High Energy ◽  
Milling Process ◽  
Particle Size Reduction ◽  
High Energy Milling ◽  
Si Nanoparticle ◽  
Si Nanoparticles

The structure and magnetic properties of Fe/Si nanoparticle prepared by high energy milling process have been examined, focusing on the phase transition. Fe/Si nanoparticles were processed by high energy milling (HEM) for 10 hours to 50 hours with a weight per cent ratio of 9:1. Based on the X-ray diffraction (XRD) pattern, transmission electron microscope (TEM) observations, and vibrating sample magnetometer (VSM) analysis, the phase transition induced by HEM, were evidenced. The effect of structural state and the particle size on the magnetic properties such as magnetization was also studied. It was found that iron and iron oxides (-Fe2O3/ Fe3O4) phase were exhibited on all milled samples. The magnetization value of Fe/Si nanoparticles increased up to 20 hours with 142 emu/gr saturated magnetization and then decreased linearly with increasing milling time. Referring to the XRD result, this decline was initially caused by the iron oxide formation and magnetic interaction between iron and iron oxides nanoparticles. The phase and magnetic properties value changes related to the interaction mechanism between Fe atoms caused by interstitial occupied of Si atoms, particle size reduction, and oxidation process.

scholarly journals Is the goal of mastication reached in young dentates, aged dentates and aged denture wearers?

2007 ◽  
Vol 99 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Anne Mishellany-Dutour ◽  
Johanne Renaud ◽  
Marie-Agnès Peyron ◽  
Frank Rimek ◽  
Alain Woda
Keyword(s):  
Particle Size ◽  
Size Reduction ◽  
Emg Activity ◽  
Particle Size Reduction ◽  
Masticatory Function ◽  
Whole Saliva ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Control Study

The objective of the present study was to assess the impact of age and dentition status on masticatory function. A three-arm case–control study was performed. Group 1 (n 14) was composed of young fully dentate subjects (age 35·6 ± 10·6 years), group 2 (n 14) of aged fully dentate subjects (age 68·8 ± 7·0 years) and group 3 (n 14) of aged full denture wearers (age 68·1 ± 7·2 years). Mastication adaptation was assessed in the course of chewing groundnuts and carrots to swallowing threshold. Particle size distribution of the chewed food, electromyographic (EMG) activity of the masseter and temporalis muscles during chewing, and resting and stimulated whole saliva rates were measured. Aged dentate subjects used significantly more chewing strokes to reach swallowing threshold than younger dentate subjects (P < 0·05), with increased particle size reduction, longer chewing sequence duration (P < 0·05) and greater total EMG activity (P < 0·05) for both groundnuts and carrots. In addition, aged denture wearers made significantly more chewing strokes than aged dentate subjects (P < 0·001) to reach swallowing threshold for groundnuts. Particle size reduction at time of swallowing was significantly poorer for denture wearers than for their aged dentate counterparts, despite an increase in chewing strokes, sequence duration and EMG activity per sequence. Masticatory function was thus adapted to ageing, but was impaired in denture wearers, who failed to adapt fully to their deficient masticatory apparatus.

scholarly journals Applying Box–Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 144
Author(s):  
Nouran S. Sharaf ◽  
Amro Shetta ◽  
Jailan E. Elhalawani ◽  
Wael Mamdouh
Keyword(s):  
Particle Size ◽  
In Vitro Release ◽  
Physicochemical Characteristics ◽  
Plga Nanoparticles ◽  
Anticancer Activities ◽  
Particle Size Reduction ◽  
Box Behnken Design ◽  
Surface Stability ◽  
The Impact

In an attempt to prove biological activity enhancement upon particle size reduction to the nanoscale, coffee (Cf) was chosen to be formulated into poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the single emulsion-solvent evaporation (SE-SE) method via Box–Behnken Design (BBD) to study the impact of certain process and formulation parameters on the particle size and size homogeneity, surface stability and encapsulation efficiency (EE%). The coffee-loaded PLGA (PLGA-Cf) NPs were characterized by different methods to aid in selecting the optimum formulation conditions. The desirable physicochemical characteristics involved small particle sizes with an average of 318.60 ± 5.65 nm, uniformly distributed within a narrow range (PDI of 0.074 ± 0.015), with considerable stability (Zeta Potential of −20.50 ± 0.52 mV) and the highest EE% (85.92 ± 4.01%). The antioxidant and anticancer activities of plain PLGA NPs, pure Cf and the optimum PLGA-Cf NPs, were evaluated using 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. As a result of nano-encapsulation, antioxidant activity was enhanced by 26.5%. Encapsulated Cf showed higher anticancer potency than pure Cf against different cancerous cell lines with an increase of 86.78%, 78.17%, 85.84% and 84.84% against MCF-7, A-549, HeLa and HepG-2, respectively. The in vitro release followed the Weibull release model with slow and biphasic release profile in both tested pH media, 7.4 and 5.5.

scholarly journals Experimental and CFD investigation of the mixing of MMA emulsion polymerization in a stirred tank reactor

2021 ◽  
Author(s):  
Shideh F. Roudsari
Keyword(s):  
Molecular Weight ◽  
Particle Size ◽  
Emulsion Polymerization ◽  
Particle Number ◽  
Polymerization Reaction ◽  
Impeller Speed ◽  
Glass Temperature ◽  
Agitation Rate ◽  
Number Density ◽  
The Impact

Although significant advances have been achieved in emulsion polymerization in recent decades, the effect of mixing on this type of polymerization has not been fully delineated yet. In fact, mixing plays a significant role in the performance of an emulsion polymerization reaction. For instance, in case of a very low agitation rate, larger droplets are generated and phase separation, which limits the diffusion mechanism, may occur. In contrast, vigorous agitation can result in reduced nucleation of particles. Therefore, the main objective of this study is to investigate the impact of mixing parameters (e.g. impeller speed, impeller type, impeller number, and baffles) on the monomer conversion, the polymer average molecular weight, particle size and size distributions, transition glass temperature, and number of particles. To achieve this objective, the emulsion polymerization of methyl methacrylate (MMA) was carried out in a lab-scale reactor equipped with a top-entry agitator, 4 wall baffles, a U shaped cooling coil, and a temperature controller. To analyze the reactive flow inside the polymerization reactor, a novel computational fluid dynamics (CFD) model was developed. The multiple reference frames (MRF) technique, k-ε model, and mixture model approach were employed to model the impeller rotation, turbulence, and multiphase flow, respectively. The particle number density distribution within the reactor was also estimated by means of the population balance approach, which employs a discrete method to describe the nucleation and growth of the polymer particles. The experimental data and CFD results showed that the installation of the baffles enhanced the particle size and molecular weight but reduced the conversion and particle number. The number density achieved using the Rushton impeller was higher than that for the pitched blade impeller. The results revealed that the effect of the impeller speed on the characteristics of the polymer attained using the pitched-blade turbine was more prominent than that for the Rushton turbine. It was also found that the impact of the impeller speed on the polymer characteristics was much more pronounced for the double pitched-blade turbines rather than for the double Rushton turbines.

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