Characterizing continuous powder mixing using residence time distribution

A review of the Residence Time Distribution (RTD) applications in solid unit operations

Effect of operating conditions and design parameters in a continuous powder mixer

An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing, primarily due to regulatory uncertainty. This paper aims to help address these concerns by introducing methods for batch definition, raw material traceability, and sensor frequency determination. All of the methods are based on established engineering and mathematical principles, especially the residence time distribution (RTD). This paper introduces a risk-based approach to address content uniformity challenges of continuous manufacturing. All of the detailed methods are discussed using a direct compaction manufacturing line as the main example, but the techniques can easily be applied to other continuous manufacturing methods such as wet and dry granulation, hot melt extrusion, capsule filling, etc.

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Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing

The objective of the study is to build a simple but informative model to describe the kinetics of layering granulation in a batch fluidized bed reactor. A cell model based on the theory of Markov chains to describe this kinetics is proposed. Several parallel chains of perfectly mixed cell according to the number of size fractions, which are under observation, were introduced. The vectors of particles volume content in the cells describe the state of the process. Evolution of the state is conditioned by particles transition from the cells of one chain to another due to their size enlargement during granulation and by particles migration along the chains due to their interaction with fluidizing gas upstream flow. The process is observed in a discrete moments of time. It is supposed that the volume of binding solution coming into a cell of a chain during one time step interacts only with the particles that can enlarge their size to transit to the cell of the next larger size fraction. The migration of the particles of a size fraction along its chain is controlled by the matrix of transition probabilities, which is different for each size fraction and depends on the total particles concentration. The model allows qualitative estimating of influence of the process parameters on the granulation kinetics. In order to validate the model, the experimental study of ammonium sulphate granulation in the lab scale fluidized bed reactor was carried out. The comparison of theoretical and experimental results was done for the example of particle size enlargement at different flow rate of the binding solution feed. A good correlation between theoretical and experimental data was found for both the mean particle size growth and the fraction size distribution at different moments of time.

/pdf/computational-and-experimental-study-of-granulation-in-4432pbu6dx.pdf

Computational and experimental study of granulation in fluidized bed reactor

/pdf/a-simple-model-to-estimate-and-compare-efficiency-of-25qeh72ugp.pdf

A simple model to estimate and compare efficiency of fluidized bed reactor without and with circulation

http://www.pphmj.com/article.php?act=art_download&art_id=12960

Theoretical and experimental study of particulate solids drying in circulating fluidized bed

Powder flow and mixing in a continuous mixer operating in either transitory or steady-state regimes: Mesoscopic Markov chain models

The objective of the study is to demonstrate theoretically one of the ways of improving the quality of continuous mixing of segregating particulate solids. The objective function of optimization is the standard deviation of segregating component distribution over the mixer's cross-section at the mixer outlet, the optimization parameter being the position of segregating component input. It is shown that the input of the component into the position that is optimized over the length of the mixer allows improving the mixing quality. The gain of optimization depends on the rate of segregation and grows with its increase.

/pdf/theoretical-study-of-optimal-positioning-of-segregating-2t887fazy5.pdf

Mizonov Vadim E

Papers

Computational and experimental study of granulation in fluidized bed reactor

A simple model to estimate and compare efficiency of fluidized bed reactor without and with circulation

Theoretical and experimental study of particulate solids drying in circulating fluidized bed

Powder flow and mixing in a continuous mixer operating in either transitory or steady-state regimes: Mesoscopic Markov chain models

Theoretical Study of Optimal Positioning of Segregating Component Input into Continuous Mixer of Solids