Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 23;100(4):1627-1632.
doi: 10.1021/acs.jchemed.3c00036. eCollection 2023 Apr 11.

Introduction to Pharmaceutical Co-amorphous Systems Using a Green Co-milling Technique

Joana F C Silva  1 , Mário T S Rosado  1 , Teresa M R Maria  1 , Pedro S Pereira Silva  2 , Manuela Ramos Silva  2 , M Ermelinda S Eusébio  1
Affiliations

Introduction to Pharmaceutical Co-amorphous Systems Using a Green Co-milling Technique

Joana F C Silva et al. J Chem Educ. .

Abstract

The concept of co-amorphous systems is introduced in an integrated laboratory experiment, designed for advanced chemistry students, using solvent-free, environmentally friendly mechanochemistry. The dual-drug naproxen-cimetidine co-amorphous system (NPX-CIM) is investigated as an example of the emergent field of medicinal mechanochemistry. Students are trained in solid-state characterization techniques including X-ray powder diffraction, Fourier-transform infrared spectroscopy, and thermal analysis by differential scanning calorimetry. This lab experiment also provides an opportunity to discuss the relevance of different solid forms of pharmaceutics, emphasizing particular properties of disordered materials. This experiment can easily fit the curriculum of any Chemistry or Pharmacy master level degree in courses dealing with instrumental analysis, solid state chemistry, or green chemistry, for classes of 6 to 18 students, in a 5-h lab session. Suggestions to adapt it to the use of a single characterization technique are provided.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Chemical structures of (a) naproxen (NPX) and (b) cimetidine (CIM).
Figure 2
Figure 2
X-ray powder diffractograms of commercial and milled NPX and CIM, and co-milled (1:1) NPX-CIM.
Figure 3
Figure 3
FTIR spectra of commercial and milled NPX, commercial and milled CIM, and co-milled (1:1) NPX-CIM.
Figure 4
Figure 4
DSC heating thermograms of commercial CIM, milled pure NPX and CIM, and co-milled (1:1) NPX-CIM mixture. β = 10 °C min–1. Small endothermic peaks visible on top of the glass transition steps are due to relaxation enthalpy, related to physical aging in the nonequilibrium glassy state.
See this image and copyright information in PMC

References

    1. Di L.; Fish P. V.; Mano T. Bridging Solubility between Drug Discovery and Development. Drug Discov. Today 2012, 17 (9), 486–495. 10.1016/j.drudis.2011.11.007. - DOI - PubMed
    1. Amidon G. L.; Lennernäs H.; Shah V. P.; Crison J. R. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability. Pharm. Res. 1995, 12 (3), 413–420. 10.1023/A:1016212804288. - DOI - PubMed
    1. Chavan R. B.; Thipparaboina R.; Kumar D.; Shastri N. R. Co Amorphous Systems: A Product Development Perspective. Int. J. Pharm. 2016, 515 (1), 403–415. 10.1016/j.ijpharm.2016.10.043. - DOI - PubMed
    1. Berry D. J.; Steed J. W. Pharmaceutical Cocrystals, Salts and Multicomponent Systems; Intermolecular Interactions and Property Based Design. Adv. Drug Delivery Rev. 2017, 117, 3–24. 10.1016/j.addr.2017.03.003. - DOI - PubMed
    1. Williams H. D.; Trevaskis N. L.; Charman S. A.; Shanker R. M.; Charman W. N.; Pouton C. W.; Porter C. J. H. Strategies to Address Low Drug Solubility in Discovery and Development. Pharmacol. Rev. 2013, 65 (1), 315–499. 10.1124/pr.112.005660. - DOI - PubMed