Saurabh Sarkar

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.

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.

On the role of forces governing particulate interactions in pharmaceutical systems: A review

Process understanding for designing, optimizing and scaling of pharmaceutical unit operations is fundamentally important to address concerns of high risks, monumental costs, and productivity decline in the pharmaceutical industry. This is especially important in the rapidly changing landscape of the pharmaceutical industry. Pharmaceutical processes majorly deal with multiphase, multicomponent flows, basics of which are discussed in terms of fundamental contact and non-contact forces. Also, basics of multiphase flow regimes, powder flow, and pertinent process modeling techniques relevant to pharmaceutical unit operations are discussed. The most fundamental contact and non-contact forces are then reviewed in detail on their molecular or physical origin, factors which influence these forces, numerical formalisms and modeling strategies to simulate flows and processes of pharmaceutical interest.

DEM modeling of high shear wet granulation of a simple system

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Differential Electrostatic Interactions between Granular Species in a Simple Hopper Chute Geometry

This article presents the findings from an experimental investigation assessing the role of different variables in determining electrostatic charges on a binary granular assembly in a simple hopper-chute set up. Several popular theories describing the generation and subsequent mitigation of static charges is reviewed and the experimental results are discussed in the light of those theories. A detailed discussion is provided on the significance of several variables considered important in the study performed under conditions representative of typical pharmaceutical manufacturing. A simple probability based model is presented which accounts for eventful contacts in a binary mixture. The theoretical arguments presented in the paper, backed by statistical analysis, lend insight into well-known but poorly understood phenomena. It is demonstrated that tribocharging of granular assemblies made of a single species on a given surface was observed in accordance with their work function difference. Mitigation of this generated charge increased linearly with concentration of addition of a second species before plateauing off at higher concentrations. The extent of charge reduction depends on interplay between the work function and hygroscopicity, and the number of contacts between the species involved.

Investigation of multiphase multicomponent aerosol flow dictating pMDI-spacer interactions

The use of Pressurized metered dose inhalers (pMDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases is frequently associated with breath-actuation synchronization problems and poor pulmonary delivery, particularly amongst the pediatric and geriatric population groups. Spacers, or Valved Holding Chambers (VHCs), are frequently used to address these problems. However, the performance of spacers with different pMDIs is also highly variable and needs to be investigated. The purpose of the current study is to develop a computational fluid dynamics (CFD) model which can characterize multiphase multicomponent aerosol flow issuing from a commercial suspension-based pMDI into a spacer. The CFD model was initially calibrated against published experimental measurements in order to appropriately model the spray characteristics. This model was subsequently used to examine several combinations of inhaler, spacer and USP Throat geometries under different discharge rates of coflow air. The CFD model predictions compared favorably with experimental measurements. In particular, the predictions show, in accordance with experimental determinations, a decrease of drug retained by the spacers with increasing coflow air. The recirculation observed near the obstructions in axial path of the spray within either spacer is considered to be central for increasing spray retention and drug deposition behavior. Fluid flow patterns within the spacers were correlated with drug deposition behavior through a dimensionless variable, the Recirculation index (RCI). Bigger particles were found to be selectively retained within the spacer.

Mechanistic investigation of mixing and segregation of ordered mixtures: experiments and numerical simulations

Abstract Pulmonary delivery of cohesive and micronized drugs through dry powder inhalers (DPIs) is traditionally achieved through the formation of ordered mixtures. In order to improve the mechanistic understanding of formation of ordered mixtures, the system consisting of micronized lactose (AZFL, representative of an active pharmaceutical ingredient) and a coarse particle carrier (LH100) is investigated as a function of different process and material variables in a high shear mixer (HSM) and in a low shear double cone (DCN) blender, using both experimental and numerical methods. Process insight is developed using a Discrete Element Method (DEM) based numerical model which could predict the formation of ordered mixtures in the two blenders and was verified against experimental determinations. Spatial and temporal evolution of granular flow are visualized and quantified in silico to reveal distinguishing features of both blenders to aid in rational selection of blenders and process parameters.

Electrostatics effects in granular materials

This purpose of this study is to investigate the role of physiochemical properties and operational conditions in determining the electrostatic interactions between two species on a surface under typical industrial conditions. The variables considered for the study were particle type, particle size and shape, loading mass, surface type, angle of inclination of chute, nature and concentration of additive. Triboelectrification of simple and binary mixtures in a simple hopper and chute geometry was observed to be strongly linked to work function and moisture content of the powdered material.