Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Polymorphic purity

09.10.2014

Surface chemistry controls the selective nucleation of crystal polymorphs of a pharmaceutical drug

Reliable batch-to-batch formation is crucial for crystalline, active pharmaceutical ingredients as two different polymorphs of the same drug may function very differently in the body. Sendhil Poornachary from the A*STAR Institute of Chemical and Engineering Sciences and colleagues now report that the surface chemistry of modified glass substrates can influence the nucleation and formation of specific polymorphs of the drug, carbamazepine, within a certain concentration range of supersaturated solutions1.


Two crystal polymorphs of the drug, carbamazepine. The tetrahedral-shaped crystals are a more energetically stable form III (top) and the needle-shaped crystals correspond to the metastable form II (bottom).

© 2014 A*STAR Institute of Chemical and Engineering Sciences

The isolation of a specific polymorph is usually achieved by controlling homogeneous crystal nucleation. However, heterogeneous nucleation — which relies on the presence of a nucleating surface — is more ‘thermodynamically favorable’, meaning less energy is required. The most common heterogeneous method is to add seed crystals to a solution, but problems such as inconsistencies in seed crystal properties and cross-nucleation between crystal polymorphs may result in unwanted polymorphs.

Poornachary and team show that modified glass surfaces can selectively nucleate two different polymorphic forms of carbamazepine, an anticonvulsant and mood-stabilizing drug. “This concept of template-induced crystallization shows promise for improving batch-to-batch reproducibility with respect to the crystal form obtained,” says Poornachary.

The researchers produced cyano-, mercapto- and fluoro-functionalized glass vials by altering the interior surface using a silanization method, and then observed crystallization of the drug from supersaturated ethanol solutions. The two polymorphs were easily distinguished; either needle-shaped crystals corresponding to the metastable form II or tetrahedral-shaped crystals of the more energetically stable form III (see image).

The researchers found that at an initial drug concentration of 60 milligrams per milliliter, the metastable form II crystals were preferentially formed on the cyano-surface with no evidence of the crystals transforming to the more stable polymorph even after 24 hours. The mercapto- and fluoro-surfaces, however, preferentially nucleated form III with a small amount of metastable form II. In control vials, both polymorphs crystallized in tandem and transformed to the stable form within 24 hours. The time taken for the first crystals to appear was similar for all three modified surfaces, and significantly faster than in the control vials.

“We plan to improve our fundamental understanding of this template-induced crystallization process through molecular modeling and simulation,” says Poornachary.

The researchers envisage that better knowledge of the molecular packing arrangements in the crystal polymorphs — along with an enhanced understanding of crystal nucleation — may enable the design of template substrates with specific chemistries, eventually improving polymorphic selectivity for a variety of active pharmaceutical ingredients.

“We are also exploring scale-up of the template-induced crystallization approach using functionalized seed crystals and template particles,” added Poornachary. 

 The A*STAR-affiliated researchers contributing to this research are from the Institute of Chemical and Engineering Sciences 

Reference

  1. Parambil, J. V., Poornachary, S. K., Tan, R. B. H. & Heng, J. Y. Y. Template-induced polymorphic selectivity: The effects of surface chemistry and solute concentration on carbamazepine crystallisation. CrystEngComm 16, 4927–4930 (2014). | article

A*STAR Research | Research SEA News
Further information:
http://www.research.a-star.edu.sg/research/7052
http://www.researchsea.com

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>