Asthma attack: Anti-inflammatory X-rayed

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  • Published: Dec 15, 2016
  • Author: David Bradley
  • Channels: X-ray Spectrometry
thumbnail image: Asthma attack: Anti-inflammatory X-rayed

Combined relief

(Left to Right): Reginald B. H. Tan, Srinivasulu Aitipamula, Annie B. H. Wong, and Pui Shan Chow. © 2016 A*STAR Institute of Chemical and Engineering Sciences

A new X-ray crystallographic study of the anti-inflammatory drug oxaprozin may lead to a new combined asthma therapy, according to research published by Singapore's Agency for Science, Technology and Research (A*STAR) in the journal RSC Advances.

Many pharmaceuticals in their original parent form often have inadequate pharmacodynamics, oral availability, solubility and other properties. As such, medicinal chemists will look for variations on the theme that improve on low water solubility for instance and so make a drug of good activity but limited availability more effective in dispersing to target sites in the body through the bloodstream. For instance, the widely used anti-inflammatory oxaprozin has limited availability. By contrast, the bronchodilator, salbutamol, widely used in so-called "reliever" inhalers for people with asthma dissolve too readily and so only has a short time in which it is active, meaning that multiple doses are often needed to keep airways open in the patient's lungs. One way to get around these problems is to combine two or more drugs in the same formulation to improve overall activity and efficacy.

As such, an exploratory study by the A*STAR team into novel solid forms of the anti-inflammatory drug oxaprozin may lead to improvements for the asthma drug, salbutamol, and help reduce inflammation of the airways giving asthma patients a chance to breathe easier.

Preventer-reliever

"With discoveries of new active pharmaceutical ingredients dwindling, combining two or more ingredients in a single dose is increasingly common for treating complex diseases such as HIV/AIDS and cancer," explains team member Srinivasulu Aitipamula of the A*STAR Institute of Chemical and Engineering Sciences. Likewise, there are many other conditions, such as the aforementioned asthma, that might benefit from this approach. "To find a more soluble version of oxaprozin that could be used in solid form, we created five novel crystalline [salts] of oxaprozin, including three molecular salts made with different organic molecules."

Aitipamula's team then used X-ray crystallography to examine each and to correlate the structures obtained with the impact on the physical and chemical properties of oxaprozin. Unfortunately, the team did not succeed in addressing the solubility issue with oxaprozin, but they did find one salt that incorporates both oxaprozin and salbutamol in the same solid and this showed great promise for creating a longer-lasting, extended-release, anti-inflammatory therapy for asthma.

"By incorporating salbutamol and oxaprozin into one solid, we were able to slow the rate of salbutamol dissolution," explains Aitipamula. "The solubility of a solid in water depends on the number of hydrogen bonds that it can form with water molecules. All the potential hydrogen bonding sites of salbutamol and oxaprozin were involved in creating the salt, meaning there were no sites left for water to interact with."

Stronger

The team explains that the resulting strong crystal lattice in the oxaprozin-salbutamol salt means that there can be a more controlled release of salbutamol over time. There is an added clinical benefit to using oxaprozin in a combined salbutamol inhaler in that patients would no longer need to take supplementary anti-inflammatory drugs, commonly corticosteroid "preventers."We will continue to expand our investigations into other active ingredients and create combined formulations for targeting different diseases," Aitipamula adds.

Related Links

RSC Adv 2016, 6, 34110: "Novel solid forms of oxaprozin: cocrystals and an extended release drug-drug salt of salbutamol"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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