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First highly elastic single-component pharmaceutical crystal demonstrated

By Frieda Wiley May 23, 2019
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(a–c) Looping of the elastic celecoxib Form III crystal and its complete recovery upon release. Credit: Chemistry of Materials

Crystals are solid structures with a homogenous makeup that exhibit specific properties as a result of their homogeneity. The mechanical properties of crystalline structures play a critical role in dictating the crystal’s dissolution rate, solubility, and other characteristics as well as the diversity of their applications. Researchers have now elucidated the elasticity of the first known single-component, bendable pharmaceutical crystal. A pharmaceutical crystal’s homogeneity helps ensure product purity as well as predictability of certain properties that contribute to the formulation of pharmaceutical products such as elasticity. The results were published in a recent issue of Chemistry of Materials.

Multi-component crystals refer to crystals that contain more than one chemical. Until now, only the elastic bending properties (ability of the crystal to completely regain its shape after being flexed or bent) of organic, multi-component crystals in the form of co-crystals or solvates or salts have been reported.

“We identified new insights into the structure–mechanical properties of organic crystals, which is of fundamental importance and can guide future designs of molecules for mechano-pharmaceutical applications,” says Changquan Calvin Sun, director of graduate studies in the department of pharmaceutics at the University of Minnesota and the study’s corresponding author.

Molecular crystals with remarkable mechanical properties are gaining attention from the scientific community because they exhibit properties of both crystals and soft matter, such as gels, polymers, and biomaterials. This makes them useful for applications in optoelectronics, actuators, sensors, and miniature devices, among others, for various medical and other applications.

The crystal studied, celecoxib Form III, was found to be a single-component (or mono-substance), elastic crystal. In the United States, celecoxib is currently marketed as the prescription drug Celebrex for inflammation and pain associated with osteoarthritis, rheumatoid arthritis, and other painful conditions. Celecoxib is also available in combination with the blood pressure drug amlodipine as Consensi—a prescription medication for people who have both high blood pressure as well as osteoarthritis.

The extent and ease with which an active pharmaceutical ingredient such as celecoxib can be milled or compressed into tablet form largely depends on the crystal’s mechanical properties. Crystals must meet certain criteria in order to be classified as “elastic with a bendable face”:

  • interlocking isotropic packing devoid of slip planes that ensure the structure remains intact by retaining its original physical features; and
  • reversible bending elasticity as a result of multiple dispersive interactions in orthogonal directions, which help ensure the crystal regains its shape after manipulation by a metallic needle.


To elucidate celecoxib’s mechanical properties, researchers conducted a series of experiments. When the crystal containing the celecoxib molecules was depressed with a metallic needle, the crystal immediately rebounded, fully intact, and resumed its original shape upon withdrawal of the needle. These findings illustrate the elastic properties of this single-component crystal.

C. Malia Reddy, a professor in the department of chemical sciences at the Indian Institute of Science Education and Research (IISER) Kolkata, India believes the soft, biologically compatible materials with mechanical durability offer an additional advantage in biological applications.

“It might be possible to install tiny needle-like, elastically flexible crystals in tissues for slow and controlled-release of solid drugs,” Reddy says.

According to Pance Naumov, associate professor of chemistry at New York University Abu Dhabi, says, “Although more studies are probably necessary to establish the correlations between elasticity with the ability to form pharmaceutical tablets, this new research sets the path to explore such correlations and more in-depth studies.”

Read the article in Chemistry of Materials.