Skip to content
Licensed Unlicensed Requires Authentication Published online by De Gruyter May 23, 2022

Pharmaceutical cocrystal consisting of ascorbic acid with p-aminobenzoic acid and paracetamol

Fatima Miles, Fayrouz Djellouli, Nourelhouda Bensiradj and Abdallah Dahmani
From the journal Physical Sciences Reviews

Abstract

As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important for global health initiatives. As a new crystal engineering strategy, cocrystals have opened a new way to modify the physicochemical properties of pharmaceutical solids. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs) without changes in the covalent chemistry have been possible through the application of binary component solids. In this work, a pharmaceutical cocrystal of ascorbic acid (A) + para-aminobenzoic acid (B) and ascorbic acid (A) + paracetamol (P) cocrystal are synthesized and characterized by PXRD, DSC, and FT-IR. FT-IR indicates the kind of interactions occurring between API and coformer. The DSC thermogram for (A–B) cocrystal showed a single endothermic peak attributed to the melting temperature at 155 °C. The thermal behavior of the cocrystal was distinct with different melting temperatures from that seen with either of the individual components; this suggests the formation of a new phase. As molecular modeling is presented as a support to the experiment, a computational study using density functional theory (DFT) at the level of the WB97XD functional and 6-311 + G (d, p) basis set was carried out using the Gaussian 09 program. This theoretical study made it possible to calculate the energetic properties, the intramolecular hydrogen bonds as well as the thermodynamic properties for the two cocrystals.


Corresponding author: Fayrouz Djellouli, Laboratoire de Thermodynamique et de Modélisation Moléculaire, Faculté de Chimie, USTHB, BP32, El-Alia, 16111 Bab-Ezzouar, Alger, Algerie, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Blagden, N, de Matas, M, Gavan, PT, York, P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 2007;59:617–30. https://doi.org/10.1016/j.addr.2007.05.011.Search in Google Scholar PubMed

2. Brittain, HG. Cocrystal systems of pharmaceutical interest: 2011. Cryst Growth Des 2012;12:5823–32. https://doi.org/10.1021/cg301114f.Search in Google Scholar

3. Jones, W, Samuel Motherwell, WD, Trask, AV. Pharmaceutical cocrystals: an emerging approach to physical property enhancement. MRS Bull 2006;31:875–9. https://doi.org/10.1557/mrs2006.206.Search in Google Scholar

4. Good, DJ, Rodriguez-Hornedo, N. Solubility advantage of pharmaceutical cocrystals. Cryst Growth Des 2009;9:2252–64. https://doi.org/10.1021/cg801039j.Search in Google Scholar

5. Naoto, S, Masatoshi, K, Kentaro, Y, Toyofumi, S, Kazuo, T, Toshiro, F. Comparison of the relative stability of pharmaceutical cocrystals consisting of paracetamol and dicarboxylic acids. Drug Dev Ind Pharm 2018;44:582–9.10.1080/03639045.2017.1405433Search in Google Scholar PubMed

6. Seato, CC, Parkin, A. Making benzamide cocrystals with benzoic acids: the influence of chemical structure. Cryst Growth Des 2011;11:1502–11. https://doi.org/10.1021/cg101403j.Search in Google Scholar

7. Walsha, D, Serrano, DR, Worku, ZA, Madi, AM, O’Connell, P, Twamley, B, et al.. Engineering of pharmaceutical cocrystals in an excipient matrix: spray drying versus hot melt extrusion. Int J Pharm 2018;551:241–56. https://doi.org/10.1016/j.ijpharm.2018.09.029.Search in Google Scholar PubMed

8. Andre, V, Fatima, M, da Piedad, M, Duarte, MT. Revisiting paracetamol in a quest for new co-crystals. CrystEngComm 2012;14:5005–14. https://doi.org/10.1039/c2ce25307k.Search in Google Scholar

9. Jain, H, Khomane, KS, Bansal, AK. Implication of microstructure on the mechanical behaviour of an aspirin–paracetamol eutectic mixture. CrystEngComm 2014;16:8471–8. https://doi.org/10.1039/c4ce00878b.Search in Google Scholar

10. Chai, JD, Head-Gordon, M. Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys Chem Chem Phys 2008;10:6615–20. https://doi.org/10.1039/b810189b.Search in Google Scholar PubMed

11. Hariharan, PC, Pople, JA. Accuracy of AH n equilibrium geometries by single determinant molecular orbital theory. Mol Phys 1974;27:209–14. https://doi.org/10.1080/00268977400100171.Search in Google Scholar

12. Frisch, MJ, Trucks, GW, Schlegel, HB, Scuseria, GE, Robb, MA, Cheeseman, JR, et al.. Gaussian 09, Revision C.01. Wallingford, CT: Gaussian Inc; 2010.Search in Google Scholar

13. Jamróz, MH. Vibrational energy distribution analysis VEDA 4 program. Warsaw; 2004.Search in Google Scholar

14. Jeffrey, GA. An introduction to hydrogen bond. Oxford University Press Inc.; 1997.Search in Google Scholar

15. Bensiradj, NH, Dekhira, A, Zouaghi, N, Ouamerali, O. DFT and TDDFT study of chemical reactivity and spectroscopic properties of M (TePh) 2 [TMEDA] M = Zn, Cd, and Hg complexes. Struct Chem 2020;31:1493–503. https://doi.org/10.1007/s11224-020-01509-9.Search in Google Scholar

16. Brinzei, M, Stefaniu, A, Iulian, O, Ciocirlan, O. Density functional theory (DFT) and thermodynamics of amino acids with polar uncharged side chains. Chem Process 2021;3:56. https://doi.org/10.3390/ecsoc-24-08420.Search in Google Scholar

17. Buddhadev, SS, Garala, KC. Pharmaceutical cocrystals – a review. Proceedings 2020;62:14. https://doi.org/10.3390/proceedings2020062014.Search in Google Scholar

18. Karagianni, A, Malamatari, M, Kachrimanis, K. Pharmaceutical cocrystals: new solid phase modification approaches for the formulation of APIs. Pharmaceutics 2018;10:18. https://doi.org/10.3390/pharmaceutics10010018.Search in Google Scholar PubMed PubMed Central

19. Khansary, MA, Shirazian, S, Walker, G. Molecular engineering of cocrystallization process in holt melt extrusion based on kinetics of elementary molecular processes. Int J Pharm 2021;601:120495. https://doi.org/10.1016/j.ijpharm.2021.120495.Search in Google Scholar PubMed

Published Online: 2022-05-23

© 2022 Walter de Gruyter GmbH, Berlin/Boston