A5053692881- Crystallization and Solubility Studies
- nanoparticles nucleation surface interactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Analytical Chemistry and Chromatography
- Spectroscopy and Quantum Chemical Studies
- Chemical and Physical Properties in Aqueous Solutions
- Crystallography and molecular interactions
- Calcium Carbonate Crystallization and Inhibition
- Drug Solubulity and Delivery Systems
- Ionic liquids properties and applications
- Freezing and Crystallization Processes
- Protein purification and stability
- Phase Equilibria and Thermodynamics
- Polymer crystallization and properties
- Surfactants and Colloidal Systems
- Material Dynamics and Properties
- Microfluidic and Capillary Electrophoresis Applications
- Process Optimization and Integration
- Membrane Separation and Gas Transport
- Molecular Junctions and Nanostructures
- Minerals Flotation and Separation Techniques
- Advanced Thermodynamics and Statistical Mechanics
- Chemical Thermodynamics and Molecular Structure
- X-ray Diffraction in Crystallography
- Enzyme Structure and Function
Massachusetts Institute of Technology
2016-2025
Novartis-MIT Center for Continuous Manufacturing
2008-2018
University of Dayton
1979-2018
University of Alabama
2015
Harvard University
2013
Novartis (Switzerland)
2011
Illinois Institute of Technology
2001-2010
Martin Luther University Halle-Wittenberg
2005-2009
Pioneer (United States)
2004-2005
Austrian Academy of Sciences
2005
Crystallization is vital to many processes occurring in nature and the chemical, pharmaceutical, food industries. Notably, crystallization an attractive isolation step for manufacturing because this single process combines both particle formation purification. Almost all of products based on fine chemicals, such as dyes, explosives, photographic materials, require their manufacture, more than 90% pharmaceutical contain bioactive drug substances excipients crystalline solid state. Hence...
The December 2011 release of a draft United States Food and Drug Administration (FDA) guidance concerning regulatory classification pharmaceutical cocrystals active ingredients (APIs) addressed two matters topical interest to the crystal engineering science communities: (1) proposed definition cocrystals; (2) as dissociable "API-excipient" molecular complexes. Indo–U.S. Bilateral Meeting sponsored by Science Technology Forum titled Evolving Role Solid State Chemistry in Pharmaceutical was...
Drug manufacturing in a fridge-sized box Commodity chemicals tend to be manufactured continuous fashion. However, the preparation of pharmaceuticals still proceeds batch by batch, partly on account complexity their molecular structures. Adamo et al. now present an apparatus roughly size household refrigerator that can synthesize and purify under continuous-flow conditions (see Perspective Martin). The integrated set modules produce hundreds thousands accumulated doses day, delivered aqueous...
A series of tubes: The continuous manufacture a finished drug product starting from chemical intermediates is reported. pilot-scale plant used novel route that incorporated many advantages continuous-flow processes to produce active pharmaceutical ingredients and the in one integrated system. As service our authors readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may be re-organized for online delivery, but not copy-edited or...
Crystallization is crucial in the pharmaceutical industry as a separation process for intermediates and final step manufacture of active ingredients (APIs). In this perspective article to celebrate 10 years Crystal Growth & Design, we focus on three areas related crystallization industry: (1) advances our understanding fundamentals nucleation, (2) production scale-up novel solid forms, (3) continuous processing. While discussed are not new, they areas, opinion, significant current interest...
Crystallization processes in the pharmaceutical industry are usually designed to obtain crystals with controlled size, shape, purity, and polymorphic form. Knowledge of process conditions required fabricate characteristics is critical during development. In this work, continuous crystallization ketoconazole, flufenamic acid, l-glutamic acid a nonconventional plug flow crystallizer was investigated. Kenics type static mixers were used promote homogeneous mixing active ingredient solution...
By switching between linear and circular polarization in the irradiation of supersaturated solutions amino acid glycine water with intense nanosecond pulses near-infrared laser light, we have obtained $\ensuremath{\gamma}$ $\ensuremath{\alpha}$ phases, respectively, through nonphotochemical light-induced nucleation (NPLIN). This is first report light controlling crystal structure. The intensity dependence NPLIN aqueous urea also reported.
We report a new photophysical phenomenon in which 1.06 \ensuremath{\mu}m pulses from Q-switched Nd:YAG laser induce crystallization supersaturated solutions of urea water. Because the are transparent at incident wavelength, photochemical mechanism is unlikely. The needle-shaped crystals that initially form tend to be aligned parallel electric field vector light, suggesting Kerr-like field-induced alignment molecules aids organizing prenucleating clusters. effect has application pump-probe...
Supersaturated aqueous solutions of glycine exposed to intense pulses plane-polarized laser light at 1.06 μm unexpectedly crystallized into the polar γ-polymorph glycine. Control not always produced crystals α-glycine, expected and most stable form. This result suggests a new approach polymorph control possibly means produce polymorphs.
Current industrial practice for control of primary nucleation (nucleation from a system without pre-existing crystalline matter) during crystallization solution involves supersaturation generation, impurity levels, and solvent composition. Nucleation behavior remains largely unpredictable, however, due to the presence container surfaces, dust, dirt, other impurities that can provide heterogeneous sites, thus making scale-up processes depend on difficult. To develop basis rational design...
Although nanoporous materials have been explored for controlling crystallization of polymorphs in recent years, polymorphism confined environments is still poorly understood, particularly from a kinetic perspective, and the role local structure substrate has largely neglected. Herein, we report use novel material, polymer microgels with tunable microstructure, polymorph solution investigating systematically effects nanoconfinement interfacial interactions on polymorphic outcomes. We show...
Active ingredients in most pharmaceutical products are complex organic molecules that require crystallization as a purification and isolation step results pure product at high process yield. Knowledge of the operating conditions required to obtain crystals with desired crystal shape, polymorph, morphology is critical during development. This paper describes two-stage mixed suspension removal (MSMPR) continuous reactive procedure developed for Aliskiren hemifumarate. was able crystallize...
An ideal pharmaceutical crystallization process produces a pure product at high yield while minimizing energy input, the equipment footprint, and its complexity. A good candidate for such is single-stage mixed-suspension, mixed-product removal (MSMPR) crystallizer with recycle (SMR) system, where characteristics of refined crystal are controlled by conditions MSMPR manipulated ratio. In this study, two continuous SMR systems, cooling cyclosporine antisolvent-cooling deferasirox, were...
This paper describes a two-stage mixed-suspension, mixed-product removal (MSMPR) continuous crystallization developed for pharmaceutical intermediate which uses anti-solvent and cooling to generate supersaturation. The results indicate that the stage in is added has significant influence on final crystal properties, while purity yield were nearly identical. population balance model was employed determine growth nucleation kinetics through parameter estimation. With incorporation of measured...
As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including large production footprint and lengthy time-scale, we previously reported refrigerator-sized continuous flow system for on-demand essential medicines. Building on this technology, herein report second-generation, reconfigurable 25 % smaller (by volume) platform featuring advances in reaction purification equipment. Consisting two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units...
This work highlights recent advances in the diagnosis, prevention, and control of impurity incorporation during solution crystallization.
Crystallization outcomes, polymorph stability rankings, and phase transformation pathways can be significantly altered when crystallization is restricted to dimensions below 1 μm. In this review, we discuss the state of art polymorphism in nanoconfinement. A primer presented regarding prevalent theories for nucleation, their implications nucleation confinement, dependence solubility on crystal size. The various methods discovery control polymorphs are reviewed. Polymorphism under...