Development and characterization of voriconazole-oxalic acid dihydrate cocrystals for enhanced pharmaceutical performance
DOI:
https://doi.org/10.56782/pps.278Keywords:
Cocrystals, liquid-assisted grinding, solubility, dissolutionAbstract
Pharmaceutical cocrystallization is a promising alternative for improving the solubility and dissolution rate or manipulating other physical properties of active pharmaceutical ingredients. The objective of this investigation was to study the effect of cocrystallization to improve physicochemical properties of voriconazole (VZ). Liquid assisted grinding method was attempted for preparation of cocrystals. Melting point, Fourier transformation infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) techniques were employed to investigate the hydrogen bonding interaction, crystallinity and thermal behaviour of prepared cocrystals respectively. The pharmaceutical cocrystals were successfully obtained with oxalic acid dihydrate (OAD) in 2:1 stoichiometric ratio. The physicochemical properties of VZ and corresponding cocrystals were assessed in terms of saturation solubility and dissolution performance. The VZ cocrystals showed enhanced solubility and dissolution rate as compared with VZ. The VZ cocrystals (4.179 mg/mL) showed higher solubility in 0.1 N hydrochloric acid than VZ (3.140 mg/mL). Cocrystals showed higher dissolution rate than VZ. The enhancement in dissolution rate of VZ cocrystal from OA was 2.28-fold within 10 min.
Downloads
References
1. Guo, M.; Sun, X.; Chen, J.; Cai, T. Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications. Acta Pharm. Sin. B. 2021, 11(8), 2537-64. doi: 10.1016/j.apsb.2021.03.030 DOI: https://doi.org/10.1016/j.apsb.2021.03.030
2. Panzade, P.; Shendarkar, G.; Shaikh, S.; Rathi, PB. Pharmaceutical cocrystal of piroxicam: design, formulation and evaluation. Adv. Pharm. Bull. 2017, 7(3), 399. doi: 10.15171/apb.2017.048 DOI: https://doi.org/10.15171/apb.2017.048
3. Singh, M.; Barua, H.; Jyothi, VG.; Dhondale, MR.; Nambiar, AG.; Agrawal, AK.; Kumar, P.; Shastri, NR.; Kumar, D. Cocrystals by design: a rational coformer selection approach for tackling the API problems. Pharm. 2023, 15(4), 1161. DOI: https://doi.org/10.3390/pharmaceutics15041161
4. Greer, ND. Voriconazole: the newest triazole antifungal agent. Bayl Univ Med Cent. 2003, 16(2), 241-8. doi: 10.1080/08998280.2003.11927910 DOI: https://doi.org/10.1080/08998280.2003.11927910
5. Scott, LJ.; Simpson, D. Voriconazole: a review of its use in the management of invasive fungal infections. Drugs. 2007, 67(2), 269-98. doi: 10.2165/00003495-200767020-00009 DOI: https://doi.org/10.2165/00003495-200767020-00009
6. Shah, MK.; Azad, AK.; Nawaz, A.; Ullah, S.; Latif, MS.; Rahman, H.; Alsharif, KF.; Alzahrani, KJ.; El-Kott, AF.; Albrakati, A.; Abdel-Daim, MM. Formulation development, characterization and antifungal evaluation of chitosan NPs for topical delivery of voriconazole in vitro and ex vivo. Polymers. 2021, 14(1), 135. doi: 10.3390/polym14010135 DOI: https://doi.org/10.3390/polym14010135
7. Sanphui, P.; Mishra, MK.; Ramamurty, U.; Desiraju, GR. Tuning mechanical properties of pharmaceutical crystals with multicomponent crystals: voriconazole as a case study. Mol. Pharm. 2015, 12(3), 889-97. Doi: 10.1021/mp500719t DOI: https://doi.org/10.1021/mp500719t
8. Kumar, SS.; Thakuria, R.; Nangia, A. Pharmaceutical cocrystals and a nitrate salt of voriconazole. CrystEngComm. 2014, 16(22), 4722-31. doi: 10.1039/C3CE42324G DOI: https://doi.org/10.1039/C3CE42324G
9. Savla, PP. The Selection and Screening of Conformers. The Bombay Technologist. 2021. doi: 10.36664/bt/2021/v68i1/164061 DOI: https://doi.org/10.36664/bt/2021/v68i1/164061
10. Wathoni, N.; Sari, WA.; Elamin, KM.; Mohammed, AF.; Suharyani, I. A review of coformer utilization in multicomponent crystal formation. Mol. 2022, 27(24), 8693. doi: 10.3390/molecules27248693 DOI: https://doi.org/10.3390/molecules27248693
11. Mushtaq, M.; Fatima, K.; Ahmad, A.; Mohamed Ibrahim, O.; Faheem, M.; Shah, Y. Pharmacokinetic interaction of voriconazole and clarithromycin in Pakistani healthy male volunteers: a single dose, randomized, crossover, open-label study. Front Pharmacol. 2023, 14, 1134803. doi: 10.3389/fphar.2023.1134803 DOI: https://doi.org/10.3389/fphar.2023.1134803
12. Marydele, J. The Merck index: an encyclopedia of chemicals, drugs and biologicals, 14th ed.; Whitehouse station (New Jeresy): Merck and Co. Inc, 2006.
13. Buddhadev, SS.; Garala, KC. Pharmaceutical cocrystals—a review. InProceedings. 2021, 62(1), 14. doi: 10.3390/PROCEEDINGS2020062014 DOI: https://doi.org/10.3390/proceedings2020062014
14. Nijhawan, M.; Godugu, M.; Saxena, T.; Farheen, T.; Dwivedi, K. Pharmaceutical co-crystals of posaconazole for improvement of physicochemical properties. Braz. J. Pharm. Sci. 2022, 58, e191024. doi: 10.1590/s2175-97902022e191024 DOI: https://doi.org/10.1590/s2175-97902022e191024
15. Ammanage, A.; Rodriques, P.; Kempwade, A.; Hiremath, R. Formulation and evaluation of buccal films of piroxicam co-crystals. Future J. Pharm. Sci. 2020, 6, 1-1. doi: 10.1186/s43094-020-00033-1 DOI: https://doi.org/10.1186/s43094-020-00033-1
16. Desai, H.; Rajadhyax, A.; Jaiswal, S.; Gulhane, N. Studies on Formulation and Evaluation of Clotrimazole Cocrystals. World j. pharm. pharm. Sci. 2022, 11(10). doi:10.20959/wjpps202210-23314 DOI: https://doi.org/10.22159/ajpcr.2021.v14i8.41857
17. Nijhawan, M.; Santhosh, A.; Babu, PS.; Subrahmanyam, CV. Solid state manipulation of lornoxicam for cocrystals–physicochemical characterization. Drug Dev Ind Pharm. 2014, 40(9), 1163-72. doi: 10.3109/03639045.2013.804834 DOI: https://doi.org/10.3109/03639045.2013.804834
18. Madan, JR.; Waghmare, SV.; Patil, RB.; Awasthi, R.; Dua, K. Cocrystals of apixaban with improved solubility and permeability: formulation, physicochemical characterization, pharmacokinetic evaluation, and computational studies. Assay drug dev techn. 2021, 19(2), 124-38. doi: 10.1089/adt.2020.1052 DOI: https://doi.org/10.1089/adt.2020.1052
19. Wu, N.; Zhang, Y.; Ren, J.; Zeng, A.; Liu, J. Preparation of quercetin–nicotinamide cocrystals and their evaluation under in vivo and in vitro conditions. RSC advances. 2020, 10(37), 21852-9. doi: 10.1039/D0RA03324C DOI: https://doi.org/10.1039/D0RA03324C
20. Khan, FM.; Ahmad, M.; Idrees, HA. Simvastatin-nicotinamide co-crystals: formation, pharmaceutical characterization and in vivo profile. Drug Des. Devel. Ther. 2020, 14, 4303-13. doi: 10.2147/DDDT.S270742 DOI: https://doi.org/10.2147/DDDT.S270742
21. Nijhawan, M.; Dhyagala, S.; Gunnam, S.; Aleti, R.; Saxena, T. Dipyridamole cocrystal tablets with enhanced solubility and dissolution at intestinal pH. Fabad J. Pharm. Sci. 2024, 49(1), 37-50. doi: 10.55262/fabadeczacilik.1318448 DOI: https://doi.org/10.55262/fabadeczacilik.1318448
22. Naqvi, A.; Ahmad, M.; Minhas, MU.; Khan, KU.; Batool, F.; Rizwan, A. Preparation and evaluation of pharmaceutical co-crystals for solubility enhancement of atorvastatin calcium. Polym. Bull. 2020, 77, 6191-211. doi:10.1007/s00289-019-02997-4 DOI: https://doi.org/10.1007/s00289-019-02997-4
23. Thimmasetty, J.; Shashank, NN.; Raheem, TA.; Shwetha, SK.; Tanmoy, G. Modafinil Cocrystals for Altered Physicochemical Properties. Res J Pharm Technol. 2021, 14(9), 4891-4896. doi: 10.52711/0974-360X.2021.00850 DOI: https://doi.org/10.52711/0974-360X.2021.00850
24. Nikam, VJ.; Patil, SB. Pharmaceutical cocrystals of nebivolol hydrochloride with enhanced solubility. J. Cryst. Growth. 2020, 534, 125488. doi: 10.1016/j.jcrysgro.2020.125488 DOI: https://doi.org/10.1016/j.jcrysgro.2020.125488
25. Thenge, RA.; Patel, R.; Kayande, NA.; Mahajan, NI. Co-crystals of carvedilol: preparation, characterization and evaluation. Int J Appl Pharm. 2020, 12(1), 42-49. doi: 10.22159/ijap.2020v12i1.35640 DOI: https://doi.org/10.22159/ijap.2020v12i1.35640
26. Colmenero, F. Mechanical properties of anhydrous oxalic acid and oxalic acid dihydrate. Physical Chemistry Chemical Physics. 2019, 21(5), 2673-90. doi: 10.1039/C8CP07188H DOI: https://doi.org/10.1039/C8CP07188H
27. Lalitha, P.; Arumugam, S.; Sinthiya, A.; Nivetha, C.; Muthuselvam, M. Oxalic acid incorporated acetamide single crystal growth dynamics, characterization, NLO and antimicrobial activities via shock wave treatment. Results in Chemistry. 2023, 5, 100790. doi: 10.1016/j.rechem.2023.100790 DOI: https://doi.org/10.1016/j.rechem.2023.100790
28. Dutt, B.; Choudhary, M.; Budhwar, V. Preparation, characterization and evaluation of fenofibrate: benzoic acid cocrystals with enhanced pharmaceutical properties. Future J. Pharm. Sci. 2021, 7(1), 170. doi: 10.1186/s43094-021-00320-5 DOI: https://doi.org/10.1186/s43094-021-00320-5
29. Ahirrao, SP.; Sonawane, MP.; Bhambere, DS.; Udavant, PB.; Ahire, ED.; Kanade, R.; Kuber, D. Cocrystal formulation: a novel approach to enhance solubility and dissolution of etodolac. Biosci. Biotechnol. Res. Asia. 2022, 19(1), 111. doi: 10.13005/bbra/2971 DOI: https://doi.org/10.13005/bbra/2971
30. Kulkarni, AL.; Shete, SW.; Hol, VI.; Bachhav, RI. Novel pharmaceutical cocrystal of telmisartan and hydrochlorothiazide. Asian J Pharm Clin Res. 2020, 13(3), 104-2. doi: 10.22159/ajpcr.2020.v13i3.36541 DOI: https://doi.org/10.22159/ajpcr.2020.v13i3.36541
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Monika Nijhawan, Bhavana Jidige, Rajeswari Aleti, Sailaja Gunnam, Trapti Saxena

This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.