Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug development: Clever crystals

20.08.2012
Water plays a key role in the co-crystallization of active pharmaceutical ingredients

There is much more to drug development than simply identifying a potent active pharmaceutical ingredient (API). Scientists must ensure that the API can tolerate the production process, remain stable during storage and distribution, and behave appropriately inside the patient’s body after administration.


Fibrous caffeine crystals as viewed by dark field light microscopy. Points where nucleation occurred are clearly visible; nucleation occurred at the points the fibrous crystals radiate out from. 1.559 ìm per pixel, the entire image covers an area of approximately 11 x 7 mm. © Zephyris

One emerging technique for improving the performance of APIs with non-ideal physicochemical properties is to co-crystallize them with a second compound that modulates their behavior. Srinivasulu Aitipamula and co-workers at the A*STAR Institute of Chemical and Engineering Sciences have now developed a novel route for preparing such co-crystals.

The researchers have discovered that adding water droplets can help to form co-crystals of caffeine, a compound known to act as a central nervous system stimulant and a muscle relaxant. Caffeine is inherently unstable to humidity — a property that can be improved by forming co-crystals with biocompatible compounds such as 4-hydroxybenzoic acid (4HBA). Computer models predict that co-crystals of caffeine and 4HBA in the ratio of 1:1 should form the most stable structure. To date, however, researchers have only been able to produce 2:1 and 1:2 co-crystals.

Aitipamula and his team have now successfully formed 1:1 co-crystals of caffeine and 4HBA, in the form of a monohydrate. By grinding together a 1:1 mixture of the two components along with two drops of water, a crystal structure was formed in which each pair of crystallization partners is partly held together by a water molecule.

According to Aitipamula, the key to water’s ability to produce the 1:1 co-crystal is its capacity to both donate and accept hydrogen bonds — the intermolecular force that holds co-crystals components together. “In the case of the caffeine-4HBA co-crystal hydrate, unused hydrogen bond acceptors and donors are satisfied by forming hydrogen bonds with the water molecule,” he says. Without water, the number of hydrogen bond donors and acceptors is unbalanced, resulting in the preferential formation of the 2:1 and 1:2 crystals instead.

The process also works for other APIs, as the researchers have found. They have generated a 1:1 co-crystal hydrate of 4HBA with piracetam, a drug used to treat memory and balance problems. The results suggest that forming hydrates offers an alternative way to generate co-crystals with particular ratios of constituents, expanding the options for forming pharmaceutical materials.

The researchers are currently focused on developing new co-crystals for APIs and studying their physicochemical properties. “Our primary emphasis is to target APIs that pose problems in pre-formulation and dissolution,” Aitipamula says.

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

References:

Aitipamula, S., Chow, P. S. & Tan, R. B. H. Co-crystals of caffeine and piracetam with 4-hydroxybenzoic acid: Unravelling the hidden hydrates of 1:1 co-crystals. CrystEngComm 14, 2381–2385 (2012).

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

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>