Solid-State Engineering for Pharmaceutical Crystallization
What is this research about?
This research focuses on the systematic understanding and control of pharmaceutical solid-state forms, including polymorphs, salts, cocrystals etc., which critically determine the physicochemical and biopharmaceutical performance of drug substances. By interrogating how molecular-level interactions translate into distinct solid forms, this work addresses a central challenge in solid-state pharmaceutics.
Why is this important?
A significant proportion of drug candidates exhibit poor aqueous solubility, making their solid-state form a decisive factor governing dissolution behavior, bioavailability, stability, and manufacturability. Different solid-state forms of the same molecule can exhibit markedly different physio-chemical properties, leading to variability in therapeutic performance. Despite its importance, solid-form selection is still frequently driven by empirical screening, underscoring the need for predictive, mechanism-informed approaches to solid-state design.
What do we do?
We conduct systematic solubility and crystallization studies on representative pharmaceutical systems to generate controlled solid-state outcomes. The resulting solids are characterized using complementary solid-state analytical techniques to establish structure-property relationships. Molecular dynamics simulations are employed to elucidate the intermolecular interactions and molecular assemblies that govern nucleation pathways and crystal growth mechanisms. These mechanistic insights are further integrated with machine learning models that relate crystallization conditions to solid-state outcomes, enabling data-driven prediction of form selection.
What is the broader goal?
The overarching objective is to establish predictive, data-enabled frameworks for solid-state form engineering, allowing rational selection and control of pharmaceutical solids during crystallization. By integrating experimental and computational approaches, this work aims to improve process consistency, reduce development timelines, and support quality-by-design strategies in pharmaceutical manufacturing.
Who is this project for?
This research is well suited for students and researchers with interests in crystallization science, solid-state and pharmaceutical chemistry, molecular simulations, data-driven modeling for applications in chemical and materials systems.
Related publications:
Characterization, Solubility, and Hygroscopicity of BMS-817399
R Prasad, S Kocevska, D Skliar, M.A. Grover, R. W. Rousseau
Org. Process Res. Dev. 2024, 28, 8, 3119–3127.
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Elucidating the Polymorphic Behavior of Curcumin during Antisolvent Crystallization: Insights from Raman Spectroscopy and Molecular Modeling
R Prasad, K.M. Gupta, S.K. Poornachary, S.V. Dalvi
Cryst. Growth Des. 2020, 20, 9, 6008–6023
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Polymorphism and Particle Formation Pathway of Carbamazepine during Sonoprecipitation from Ionic Liquid Solutions
R. Prasad, K. Panwar, J. Katla, S.V. Dalvi
Cryst. Growth Des. 2020, 20, 8, 5169–5183
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Precipitation of curcumin by pressure reduction of CO2-expanded acetone
R Prasad, R. Patsariya, S.V. Dalvi
Powder Tech. 2017, 310, 143-153
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External Field Driven Control of Crystallization Processes
What is this research about?
This research examines how external physical fields can be applied to modulate crystallization processes in advanced solvent systems, with a focus on their influence on nucleation kinetics, crystal growth, orientation, and resulting solid-state form. By introducing external fields during crystallization, this project seeks to move beyond thermodynamic control alone and incorporate kinetic pathways as active design variables.
Why is this important?
Crystallization outcomes are often governed by complex kinetic phenomena, including mass transport, interfacial processes, and molecular organization at the crystal-solution interface. External fields such as ultrasound or electric fields provide non-chemical means to perturb these phenomena by enhancing molecular mobility, altering local supersaturation, influencing charged or polar species, and modifying transport processes. When combined with advanced solvents such as ionic liquids which are characterized by high ionic conductivity and tunable solvation environments, external fields offer a powerful platform for accessing crystallization regimes and solid-state forms that are difficult to achieve under conventional conditions.
What do we do?
We design and conduct field-assisted crystallization experiments by systematically varying field conditions and solvent environments, followed by solid-state characterization to understand how external fields influence molecular transport, nucleation behavior, and growth mechanisms.
What is the broader goal?
The broader objective is to develop external-field-enabled crystallization strategies that expand the accessible crystallization design space and enable control of solid-state outcomes for pharmaceutical and materials engineering applications.
Who is this project for?
This project is well suited for students and researchers interested in crystallization science, solid-state chemistry, pharmaceutical and materials engineering, process intensification, and the application of physical fields to control structure formation in complex material systems.
Related publications:
Sonocrystallization: Monitoring and controlling crystallization using ultrasound
R. Prasad, S.V. Dalvi
Chem. Eng. Sci. 2020, 226, 115911
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Understanding Morphological Evolution of Griseofulvin Particles into Hierarchical Microstructures during Liquid Antisolvent Precipitation
R. Prasad, S.V. Dalvi
Cryst. Growth Des. 2019, 19, 10, 5836–5849
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Polymorphism and Particle Formation Pathway of Carbamazepine during Sonoprecipitation from Ionic Liquid Solutions
R. Prasad, K. Panwar, J. Katla, S.V. Dalvi
Cryst. Growth Des. 2020, 20, 8, 5169–5183
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Online Process Monitoring and Control of Slurry-Based Systems
What is this research about?
Process Analytical Technology (PAT) refers to a suite of in-situ real-time measurement and analysis approaches designed to provide direct insight into evolving process and material attributes during manufacturing. This research project advances PAT methodologies for online characterization of slurries and particulate systems, with particular emphasis on capturing the dynamic evolution of solid-phase properties in chemical and pharmaceutical processes.
Why is this important?
Key solid-phase attributes, including particle size distribution and solids concentration, exert strong control over process performance, product quality, and downstream operations such as filtration, drying, and formulation. Despite their importance, these attributes are often inferred from offline or indirect measurements, limiting temporal resolution and obscuring transient phenomena. The absence of real-time information limits process understanding and hampers effective control, especially in inherently dynamic operations such as crystallization.
What do we do?
We develop and integrate PAT-based monitoring strategies capable of extracting quantitative information on solid-phase properties directly from operating processes. These in-situ measurements are coupled with regression-based and data-driven modeling frameworks to translate raw PAT signals into physically meaningful indicators of particle size, solids content, and overall process state.
What is the broader goal?
The broader objective is to establish robust and predictive PAT frameworks that enable real-time monitoring and control of particulate processes, supporting quality-by-design principles and improved process robustness.
Who is this project for?
This research is well suited for students and researchers interested in process analytical technology, crystallization and particulate systems, spectroscopy, data-driven modeling, and advanced strategies for real-time process monitoring and control in pharmaceutical and chemical engineering.
Related publications:
Quantifying Dense Multicomponent Slurries with In-Line ATR-FTIR and Raman Spectroscopies: A Hanford Case Study
R. Prasad, S.H. Crouse, R.W. Rousseau, M.A. Grover
Ind. Eng. Chem. Res. 2023, 62, 39, 15962–15973
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Real-time infrared spectroscopy coupled with blind source separation for nuclear waste process monitoring
S.H. Crouse, S. Kocevska, S. Noble, R. Prasad, A.M. Howe, D.P. Lambert, R.W. Rousseau, M.A. Grover
Front. Nucl. Eng. 2023, 2, 1295995.
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