Mitigation of Tribocharging in Pharmaceutical Powders using Surface Modified V-Blenders.

INTRODUCTION: The pharmaceutical industry involves handling of powders on a large scale for manufacturing of solid dosage forms such as tablets and capsules constituting about 85% of the dosage forms. During this manufacturing process, powders get electrostatically charged due to numerous particle-particle and particle-equipment wall collisions. Most of the pharmaceutical powders are insulators in nature and they accumulate charge for longer durations making it difficult to dissipate the generated charge. In this study, a surface modified blender has been used to analyze tribocharging in pharmaceutical powders. METHODS: The surface modified blender has been fabricated using two types of materials, an insulator, and a conductor. The conductor or the metal arm induces charge of opposite polarity to that of the charge induced by the insulator arm and the overall charge on the powder decreases during the tumbling motion of the blender. Ibuprofen was used as the model drug and processed in aluminum, polyvinyl chloride (PVC), stainless steel, surface modified aluminum-PVC (Al-PVC) and surface modified stainless steel- PVC (SS-PVC) blender at 20% RH for different blending times such as 2, 10, 20, 30 and 40 min. To better understand the tribocharging phenomenon in surface modified V blenders, an experimentally validated computational model was developed using Discrete Element Method (DEM) modeling. RESULTS: Significant reduction (> 50%) in electrostatic charge was observed for Ibuprofen using surface modified blenders in comparison to metal only and insulator only V blenders. Additionally, an identical charging trend was observed between the simulation and experimental data.  CONCLUSION: It was established that careful selection of equipment materials could significantly reduce the electrostatic charging of pharmaceutical powders and DEM model could be a really useful tool in assessing the applicability of the modified V blenders.

Impact of powder-binder interactions on 3D printability of pharmaceutical tablets using drop test methodology.

In this study, a pre-screening test has been developed for the binder-jet 3D printing process (BJ3DP) which has been validated using statistical analysis. The pre-screening test or drop test has been adapted from the wet granulation field and modified later on to be used for tablet manufacturing in BJ3DP. Initially, a total of eight powders and ten water-based binder solutions have been introduced in the preliminary test to understand the powder-binder interactions. Afterward, based on the preliminary test results, three blends were developed which had undergone the same drop test. All these powder and binder combinations were then used for 3D printing. The key parameters such as mechanical strength and shape factors of the drop test agglomerates and 3D printed tablets were then compared using multiple linear regressions. Few dimensionless parameters were introduced in this study such as binding capacity and binding index to capture the printability properties of the powders used in this study. Significant relations (p<0.05) were found between the drop test and the BJ3DP process. Application of drop test was carried out to establish a prescreening test, ii) to develop new blend formulations as well as iii) to develop a fundamental understanding of powder-binder interaction during BJ3DP process.

Discrete Element Modeling (DEM) based investigation of tribocharging in the pharmaceutical powders during hopper discharge.

Triboelectric charging is defined as the phenomenon of charge transfer between two different material surfaces when they are brought into contact and separated. The focus of this research is the development of a Discrete Element Method (DEM) based simulation model to predict tribocharging during hopper discharge. Due to decreased particle-wall interactions and reduced particle wall contact times, net charges generated during hopper discharge are low. The simulation model confirmed this effect and was implemented to predict the triboelectric behavior of glass beads and MCC particles during hopper flow, along with the prediction of percent charged and uncharged particles. Approximately one-third of the particles were predicted to remain uncharged during the hopper discharge simulations for mono-dispersed particles, thus rendering a comparatively high amount of charge distribution into a small concentration of materials. The DEM model acted as a tool to predict charges that can be generated during hopper discharge at a specified geometry, with a potential to mitigate particle charging, when used for appropriate selection of hopper angles, and hopper wall materials.

A Simplex Centroid Design to Quantify Triboelectric Charging in Pharmaceutical Mixtures.

The present study focuses on the implementation of a modified simplex centroid statistical design to predict the triboelectrification phenomenon in pharmaceutical mixtures. Two drugs (Ibuprofen and Theophylline), 2 excipients (lactose monohydrate and microcrystalline cellulose/MCC), and 2 blender wall materials (aluminum and poly-methyl methacrylate) were studied to identify the trends in charge transfer in pharmaceutical blends. The statistical model confirmed the excipient-drug interactions, irrespective of the blender wall materials, as the most significant factor leading to reduced charging. Also, lactose monohydrate was able to explain the charge variability more consistently compared with MCC powders when used as secondary material. The ratio of the individual components in the blends explained almost 80% of the bulk charging for Ibuprofen mixtures and 70% for Theophylline mixtures. The study also explored the potential lack of efficacy of lactose-MCC as a combination in ternary systems when compared with binary mixtures, for impacts on charge variability in pharmaceutical blends.

Quantification of Moisture-Induced Cohesion in Pharmaceutical Mixtures.

Moisture-induced flow variabilities in pharmaceutical blends lead to multiple impediments during manufacturing of solid dosage formulations. Processing and storage humidity conditions both govern the moisture contents of the pharmaceutical mixtures and bear significant impact on the final product quality. In this study, experimentally validated discrete element method-based computational models along with statistical formalism have been implemented to develop a predictive tool for moisture-induced cohesion in binary and tertiary mixtures. V-blending was applied to prepare the pharmaceutical blends, and mixing characterization was performed using a Raman PhAT probe. Optimum fill volume was established for the mixing conditions to minimize static charging due to blender wall interactions on the pharmaceutical powders. A simplex-centroid (augmented) design for 3-component system was implemented to predict and quantify the nonlinear behavior of moisture-induced cohesion between the pharmaceutical powders based on their systematic hopper discharge studies (experiments and simulations). A methodical implementation of these quantification tools was hence performed to validate a design space that enables an approach to the appropriate selection of blend concentrations that achieve minimum mixture flow variability across different humidity conditions.

DEM based computational model to predict moisture induced cohesion in pharmaceutical powders.

Pharmaceutical powder flow can alter significantly based on the exposed humidity conditions, and lack of computational models to predict the same may undermine process development, optimization, and scale-up performances. A Discrete Element Model (DEM) is proposed to predict the effects of humidity on pharmaceutical powder flow by altering the cohesive forces based on granular bond numbers in simple hopper geometries. Experiments analogous to the simulations are further performed for three commonly used pharmaceutical excipients at 20%, 40% and 60% RH. The equivalent DEM based bond numbers to predict the powder flow tendencies are in good accordance with the experimental results and can be a useful tool to predict the outcomes of different pharmaceutical processing techniques at various humidity conditions.

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.

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.