Bodhisattwa Chaudhuri

A combined experimental and numerical approach to explore tribocharging of pharmaceutical excipients in a hopper chute assembly

Electrostatic charging via contact electrification or tribocharging refers to the process of charge transfer between two solid surfaces when they are brought into contact with each other and separated. Charging of continuous particulate flows on solid surfaces is poorly understood and has often been empirical. This study aims toward understanding the tribocharging of pharmaceutical excipients using a simplified geometry of unidirectional flow in a hopper-chute assembly. Assuming electron transfer to be the dominant mechanism of electrification, a triboelectric series was generated using work functions estimated from quantum chemical calculations. A 3D-DEM model has been developed employing charge transfer and electrostatic forces. Using numerical simulations, the charge accumulation for an assemblage of particles during flow was determined under different conditions. To theoretically analyze the process of charging, parametric studies affecting powder flow have been investigated. A higher specific charge was observed at larger friction coefficients and lower restitution coefficients. The results obtained from the simulation model reinforce the collisional nature of triboelectrification. The simulation results revealed similar trends to experimental observations. However, to enable a priori prediction the model needs to be tested for additional materials or extended to other process operations.

Contact drying: a review of experimental and mechanistic modeling approaches.

Drying is one of the most complex unit operations with simultaneous heat and mass transfer. The contact drying process is also not well understood as several physical phenomena occur concurrently. This paper reviews current experimental and modeling approaches employed towards a better understanding of the contact drying operation. Additionally, an overview of some fundamental aspects relating to contact drying is provided. A brief discussion of some model extensions such as incorporation of noncontact forces, interstitial fluids and attrition rate is also presented.

Experiments and numerical modeling to estimate the coating variability in a pan coater

The purpose of this work is to investigate the effect of the coating process parameters on coating performance and coating variability, and hence determine the optimal operating conditions. Coating of particles is done to mask the unpleasant taste or odor of the drug, to control the bioavailability of the API, and to increase shelf-life. The coating solution is sprayed in specific locations of the granular bed and coating uniformity is achieved by interparticle collisions and overall mixing behavior in the coater. Thus, good understanding of particle flow and granular mixing in a pan coater is vital to optimize the process parameters to reduce coating variability. Coating experiments are performed at previously determined optimal mixing conditions using Lactose nonpareils. The coating fluid (aqueous solution of Opadry II) is sprayed intermittently at different flow rates and concentration. Vernier Caliper is used to measure the change in diameter and the coating of the particles. Moreover, DEM based numerical modeling of spray coating is also performed for same operational parameter set and spray characteristic (center and the radius of the spray zone) used in the experiments. DEM simulation provides the residence time distribution of all the particles passing through the spray zone. The coating variability in the experiments is estimated at different pan and spray variables. The coating variability decreases with the increase inpan tilt, coating time and an optimum speed. The spray characteristics does not seem to have much effect on the variability although better coating is observed under better mixing conditions of high tilt and pan speed for the same spray parameters. The mass distribution of coated particles is quantified in the numerical model by the total number of particles passing through the spray zone and also by the frequency distribution of the residence time of the coated particles. It is observed that the simulations are in good agreement with the experiments for the effect of orientation (tilt) of the pan coater on coating variability. However simulations over predicted the effect of speed as compared to the experiments to reach the minimum coating variability. In the current study, the experimental setup did not reflect the typical bead coating setup used in the industry; rather depict a simplified setup to validate the numerical model.

Triboelectrification: A review of experimental and mechanistic modeling approaches with a special focus on pharmaceutical powders

The continuous relative motion of particles against solid surfaces in pharmaceutical manufacturing triggers multiple physio-chemical alterations generating contact charging or triboelectrification. Charged particles in manufacturing processes can actuate multiple impediments including agglomeration, segregation during flow or adhesion to process equipment. Generation of excess charge might lead to electrostatic discharges inducing severe imperilments of fire and explosions. Despite its prevalence, the electrostatic charging process is not fully understood, owing to the diverse physical, chemical and environmental factors that can affect the phenomenon. In the course of this review, some of the basic concepts involved in charge transfer have been briefly discussed highlighting the different experimental approaches employed in measuring electrostatic charges and summarizing the constituent factors responsible. Pertinent numerical models have been further conferred to analyze the different hypotheses of particle charging.

Magnetically mediated flow enhancement for controlled powder discharge of cohesive powders

Abstract A new flow enhancement system is developed for cohesive powders. It is based on the concept of multiple, point source, internal excitations. In this system, a mass of small permanent-magnetic particles are placed in the discharge zone of a hopper, and then an oscillating magnetic field is applied to excite these magnets. A screen is placed at the exit to keep the magnets within the hopper. The magnetic particles spin furiously, go though random collisions with each other, and agitate the mass of cohesive powder near the exit of the hopper. As a result, the internal structure of the cohesive powder is disrupted and the powder gets fluidized and demonstrates an increased flowability. This device, called the magnetically assisted powder flow (MAPF) system, has been investigated for discharging cohesive powder from a hopper. It is shown that this device is capable of a controlled powder discharge, which is a linear function of time. The effects of various parameters, such as the amount and size of the magnetic particles and the magnetic field strength on the discharge rate are investigated. The operating principle of this device is different from conventional flow enhancement devices such as pneumatic, vibrational, or mechanical systems because powder “fluidization” is generated through random motion of the magnetic particles within the powder, and the presence of the screen prevents flooding. Modeling of the motion of the magnetic particles under the influence of an oscillating field is considered to show how the spinning and random translations occur in such a system. Discrete element modeling of a system of magnetic particles is also carried out to show the effect of various parameters on fluidization. This system can be applied for other powder technology applications, for example, the measurement of angle of repose for cohesive powders.

Experimental and model-based approaches to studying mixing in coating pans

The focus of this study was the determination of mixing patterns and rates inside a cylindrical coating pan. The research for this study was divided into two parts. The first part examined the mixing pattern and the movement of tablets inside of a coating pan experimentally. The second part consisted of using a DEM (Discrete Element Model) simulation to evaluate mixing in the coating pan in silico. Mixing was investigated as a function of the rate of rotation of the pan and the number of revolutions. Mixing rates were measured in two directions – axial – from the front of the unit to the back of the unit along its axis and radial/angular – in the plane orthogonal to its axis. Radial/angular mixing was faster than axial mixing – the coating pan was found to be well-mixed across the axis within 2–8 revolutions as compared to 16–32 revolutions needed for the pan to be well-mixed along the axis. The DEM simulation used for this study is capable of predicting how fast the tablets mix in the coating pan. It does so by explicitly modeling the motion of individual tablets in the unit. Model predictions were verified by comparing the simulated mixing in the coating pan to the experiments. The simulated mixing process is found to be slightly slower than the experimentally observed mixing, which means that the simulations give a conservative estimate of mixing rates. The model can also be used to calculate the residence time distribution of the tablets in a spray zone of a given area.

Quantifying Dry Milling in Pharmaceutical Processing: A Review on Experimental and Modeling Approaches

Particle size reduction by mechanical means is an important unit operation in the pharmaceutical industry, used to improve flow, solubility, and in amorphization of drugs. It is usually achieved by the fracturing of particles under the action of applied energy. Despite being pervasive in the pharmaceutical field, it is one of the least understood processes owing to the complexity of material and process variables involved during milling. To comprehend the process, efforts should be focused on techniques that measure the particle size as well as the control the process. With the ongoing initiative of US FDA to encourage design in quality, the review is focused on some process analytical tools to characterize particle size distribution as well as process modeling tools to simulate particle size reduction. Additionally, an overview of some fundamental aspects related to milling is provided. To this end, the review is limited, mainly concentrating on some of experimental and modeling approaches used to quantify and understand the physics behind the process of dry milling.

Quantification of Tribocharging of Pharmaceutical Powders in V-Blenders: Experiments, Multiscale Modeling, and Simulations

Pharmaceutical powders are very prone to electrostatic charging by colliding and sliding contacts. In pharmaceutical formulation processes, particle charging is often a nuisance and can cause problems in the manufacture of products, such as affecting powder flow, fill, and dose uniformity. For a fundamental understanding of the powder triboelectrification, it is essential to study charge transfer under well-defined conditions. Hence, all experiments in the present study were conducted in a V-blender located inside a glove box with a controlled humidity of 20%. To understand tribocharging, different contact surfaces, namely aluminum, Teflon, poly methyl methacrylate, and nylon were used along with 2 pharmaceutical excipients and 2 drug substances. For the pharmaceutical materials, the work function values were estimated using MOPAC, a semiempirical molecular orbital package which has been previously used for the solid-state studies and molecular structure predictions. For a mechanistic understanding of tribocharging, a discrete element model incorporating charge transfer and electrostatic forces was developed. An effort was made to correlate tribocharging of pharmaceutical powders to properties such as cohesive energy density and surface energy. The multiscale model used is restricted as it considers only spherical particles with smooth surfaces. It should be used judiciously for other experimental assemblies because it does not represent a full validation of a tightly integrated model.

Experimental and modeling approaches in characterizing coating uniformity in a pan coater: A literature review

This review provides a comprehensive record of experimental and modeling approaches that can be used to study the effect of critical process parameters affecting the coating uniformity in pharmaceutical coating operation. Explicit reference is given to the development of the approach and its previous usage with particular emphasis on the advantages, limitations and model assumptions.

Development of a Rational Design Space for Optimizing Mixing Conditions for Formation of Adhesive Mixtures for Dry-Powder Inhaler Formulations

The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated.