Research Projects

Rationale of the research and scientific gaps in the area: Origin of electrostatic surface charges in bulk pharmaceutical materials during handling and mechanized processes remains poorly understood, despite the wide spread prevalence of the issue in chemical industry. Although it is well known that pharmaceutical materials (insulators) easily accumulate surface charge, there is no means to predict it, causing multiple impediments in drug development process. Generally, charged particles can lead to obstructions including agglomeration, segregation during flow or adhesion to process equipment, thereby impairing flowability, surface energetics, and compaction properties. Conversely, surface charges can be advantageous in certain context, like promoting homogeneous powder blending and enhancing efficiency in pulmonary drug delivery. This suggests that prediction of surface charges can be highly beneficial to mitigate charge-induced complications and optimize drug delivery performance. The electrostatic charge accumulation in pharmaceuticals is typically attributed to triboelectricity and is considered difficult to regulate due to lack of molecular level understanding. In this context, our group for the first time provided an atomic structural basis for the generation of colossal surface charges on mechanically impacted molecular crystals. For last few years we have been extensively exploring the evolution of electrostatic charges on molecular crystals and the effects in various fields, with a special focus on APIs. While most of the charge related issues are resolved in industry on an empirical basis, it should be possible to predict the occurrence of charges from the knowledge of crystal structure and symmetry. Our systematic study will guide us towards a much more methodical approach to adjust the processing conditions, making the overall process highly efficient in terms of time and money. This brings us to a stage to test them in potential applications, for e.g., its influence on bulk processing and drug delivery mechanism of dry powder inhalers. As the physicochemical properties of dry powder inhaler particles are known to be significantly influenced by the electrostatic surface charges, controlling the charge generation can have an immense effect on their aerodynamic properties. Since such work demands the integration of diverse subjects, namely, crystal engineering, materials science, pharmaceutical sciences, we are in a strong position to lead this topic and demonstrate the consequences of mechanically induced surface charges in drug delivery processes. Hypothesis: Our recent studies suggest that crystal symmetry plays a key role in the generation of surface charges. Absence of centrosymmetry in crystalline forms is more critical than the polarity of the molecules or heteroatoms. We hypothesize that these factors should be very useful for understanding, predicting and controlling the surface charges in bulk chemicals including APIs. To attain our goal, we will go through a multistep approach to understand the fundamentals of surface charges and its implications to bulk processing and efficient drug delivery. We will explore suitable API systems by mining the Cambridge Crystallographic Data Centre database. The emergence of mechano-induced surface charges will be investigated by performing fracture tests on the selected API systems with distinct crystal structure and symmetry. The surface charges will be probed by Kelvin probe force microscopy and the surface energetics (dispersive and polar) will be characterized by inverse gas chromatography. The insights of the structure-property correlations will be further utilized to optimize the bulk processing behavior of inhaler solids and their aerodynamic properties for efficient drug delivery. The outcome of this project will help to predict and optimize electrostatic charges which will reduce manufacturing cost and avoid any adversities during processing and manufacturing.