Surface chemistry offers new approach to directing crystal formation in pharmaceutical industry

March 9, 2016
Surface chemistry offers new approach to directing crystal formation in pharmaceutical industry
Temperature–concentration phase diagrams aid planning of crystallization processes on an industrial scale. Credit: The Royal Society of Chemistry. 

A study by A*STAR researchers suggests the surface properties of the glass vessels in which pharmaceutical ingredients are prepared has an effect on how they crystallize.

When deciding how to control crystallization of an active ingredient during large scale production, drug companies consider many parameters such as solvent type, solute concentration and temperature to ensure the right crystal form.

Different crystal forms (polymorphs) of exhibit different physicochemical properties and can behave very differently once inside the body, so reliable production of the required polymorph is vital.

In 2014, Sendhil Poornachary at the A*STAR Institute of Chemical and Engineering Sciences and colleagues showed that the surface chemistry of modified glass vials influences nucleation and growth of selective crystal polymorphs of the anticonvulsant drug carbamazepine. While needle-shaped crystals preferentially formed in the cyano-functionalized vials, tetrahedral-shaped crystals formed in those modified with fluoro- and mercapto-groups. A mixture of the two forms was crystallized inside a control (unmodified) glass vial.

Now, the team has extensively studied the temperature ranges and solute concentrations at which the crystallization of carbamazepine occurs on different chemically-modified surfaces1. By observing the crystal polymorph formed in these vials at a given temperature and concentration, the polymorph occurrence regions were plotted on a temperature–concentration phase diagram (see image). "This type of representation is important to the pharmaceutical industry in the context of defining the design space for a robust crystallization process development," Poornachary says.

The impact of surface chemistry on the crystallization process was then investigated with the help of molecular models. "The experimental results were correlated with the results from a molecular modeling study, which revealed that specific chemical interactions between the crystal structure and functional groups on the template surface promoted nucleation of a particular polymorph," explains Poornachary.

"We envisage that the insights from this work will help develop in silico models to predict the crystallization of [any] active pharmaceutical ingredient on a given template surface," he adds. It is also hoped that surfaces that promote selective nucleation of crystal forms may enable greener, aqueous solvents to be used in a wider range of crystallizations.

Next, the team plans to test the use of functionalized templates to direct the crystallization of carbamazepine on a larger scale. "Potential design approaches for template-induced development could include forced flow through functionalized glass capillaries or using functionalized template particles as seeds, rather than the functionalized vessels we have used for this work."

Explore further: Water plays a key role in the co-crystallization of active pharmaceutical ingredients

More information: Jose V. Parambil et al. Establishing template-induced polymorphic domains for API crystallisation: the case of carbamazepine, CrystEngComm (2015). DOI: 10.1039/c5ce01080b

Related Stories

Watching protein crystal nucleation in real time

January 21, 2015

A major hurdle in structural biology and pharmacology is growing crystals to determine the structure of the biomolecules and pharmaceuticals under study. Researchers at the University of Tübingen, working with colleagues ...

Crystal studies reveal malaria's weak spots

April 3, 2015

(—The World Health Organization's 2014 report on worldwide malaria cases showed that while there has been a significant decrease in the incidence of malaria, overall, there were still 198 million cases reported ...

Cold crystallization has a dual nature

July 22, 2015

In some vitrous substances, when heated, not one, but two physical mechanisms are reponsible for crystallization, as scientists working at the Insitiute of Nuclear Physics in Krakow, Poland, have discovered. The first-time ...

Recommended for you

New electrical energy storage material shows its power

August 24, 2016

A powerful new material developed by Northwestern University chemist William Dichtel and his research team could one day speed up the charging process of electric cars and help increase their driving range.

Calcium channel blockers caught in the act at atomic level

August 24, 2016

An atomic level analysis has revealed how two classes of calcium channel blockers, widely prescribed for heart disease patients, produce separate therapeutic effects through their actions at different sites on the calcium ...

Bio-inspired tire design: Where the rubber meets the road

August 24, 2016

The fascination with the ability of geckos to scamper up smooth walls and hang upside down from improbable surfaces has entranced scientists at least as far back as Aristotle, who noted the reptile's remarkable feats in his ...

Selecting the right house plant could improve indoor air

August 24, 2016

Indoor air pollution is an important environmental threat to human health, leading to symptoms of "sick building syndrome." But researchers report that surrounding oneself with certain house plants could combat the potentially ...

LiH mediates low-temperature ammonia synthesis

August 24, 2016

Nearly half of the world's population is fed by industrial N2 fixation, i. e., the Harbor-Bosch process. Although exergonic in nature, NH3 synthesis from N2 and H2 catalyzed by the fused Fe has to be conducted at elevated ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.