Preparation and Characterization of Fluconazole- Resorcinol Co-crystal

  • Fikri Alatas Alatas Fakultas Farmasi, Universitas Jenderal Achmad Yani
  • Hestiary Ratih Fakultas Farmasi, Universitas Jenderal Achmad Yani
  • Titta Hartyana Sutarna Fakultas Farmasi, Universitas Jenderal Achmad Yani
  • Yoga Windu Wardhana 2Fakultas Farmasi, Universitas Padjadjaran
  • Dini Tereslina Fakultas Farmasi, Universitas Jenderal Achmad Yani
  • Sundani Nurono Soewandhi 3Sekolah Farmasi, Institut Teknologi Bandung


Fluconazole (FLU), an oral antifungal widely used in the treatment of vaginitis and
candidiasis, is known to have low bioavailability due to its low solubility. The purpose of this study
was to prepare and characterize co-crystal fl uconazole-resoscinol (FLU-RES). The preparation of
co-crystal was performed by grinding together the equimolar mixture of FLU-RES which is dripped
with a few ethanol. Powder X-ray diff raction, diff erential scanning calorimetry (DSC), and polarized
microscopy methods were performed to characterize the formation of FLU-RES co-crystal. Relevant
physicochemical properties include solubility tests in water and dissolution tests in pH 1.2; 4.5 and
6.8 buff er solution. The powder X-ray diff ractogram of FLU-RES milled result showed the presence
of new peaks and loss of the main peaks of FLU and RES. The characterization of grinding result by
DSC and polarized microscopy methods also showed the co-crystal formation between FLU and RES.
The solubility of FLU-RES co-crystal in water is solubility two folds more than pure FLU, while its
dissolution rate is 1.67-1.72 times faster than pure FLU.


1. Qiao N, Li M, Schlindwein W, Malek N, Davies A,
Trappitt G. Pharmaceutical cocrystals: An overview.
Vol. 419, International Journal of Pharmaceutics.
2011. 1–11.

2. Trask A V., Motherwell WDS, Jones W. Physical stability
enhancement of theophylline via cocrystallization. Int
J Pharm. 2006;320(1–2):114–23.

3. Chen Y, Li L, Yao J, Ma YY, Chen JM, Lu TB.
Improving the solubility and bioavailability of
apixaban via apixaban-oxalic acid cocrystal. Cryst
Growth Des. 2016;16(5):2923–30.

4. Shaikh R, Singh R, Walker GM, Croker DM.
Pharmaceutical Cocrystal Drug Products : An Outlook
on Product Development. Trends Pharmacol Sci. 2018.

5. Vishweshwar P, Mcmahon JJA, Bis J a., Zaworotko
MJ. Pharmaceutical co-crystals. J Pharm Sci.

6. Kastelic J, Lah N, Kikelj D, Leban I. A 1:1 cocrystal of
fluconazole with salicylic acid. Acta Crystallogr Sect
C Cryst Struct Commun. 2011;67(9):370–2.

7. Kastelic J, Hodnik Ž, Šket P, Plavec J, Lah N, Leban I,
et al. Fluconazole cocrystals with dicarboxylic acids.
Cryst Growth Des. 2010;10(11):4943–53.

8. Dayo Owoyemi BC, Da Silva CCP, Souza MS, Diniz
LF, Ellena J, Carneiro RL. Fluconazole: Synthesis and
structural characterization of four new pharmaceutical
co-crystal forms. Cryst Growth Des. 2019;19(2):648–

9. Sanphui P, Goud NR, Khandavilli UBR, Nangia A.
Fast dissolving curcumin cocrystals. Cryst Growth
Des. 2011;11(9):4135–45.

10. Gangavaram S, Raghavender S, Sanphui P, Pal S,
Manjunatha SG, Nambiar S, et al. Polymorphs and
cocrystals of nalidixic acid. Cryst Growth Des.

11. Karki S, Friščić T, Fábián L, Jones W. New solid forms
of artemisinin obtained through cocrystallisation.
CrystEngComm. 2010;12(12):4038.

12. Qiao N, Li M, Schlindwein W, Malek N, Davies A,
Trappitt G. Pharmaceutical cocrystals: An overview.
Int J Pharm. 2011;419(1–2):1–11.
Jurnal Ilmu Kefarmasian Vol 18, 2020 Indonesia 183

13. Cerreia Vioglio P, Chierotti MR, Gobetto R.
Pharmaceutical aspects of salt and cocrystal forms of
APIs and characterization challenges. Adv Drug Deliv
Rev. 2017;117:86–110.

14. Hasa D, Jones W. Screening for new pharmaceutical
solid forms using mechanochemistry: A practical guide.
Adv Drug Deliv Rev. 2017;117:147–61.

15. Shan N, Toda F, Jones W. Mechanochemistry and cocrystal
formation: eff ect of solvent on reaction kinetics.
Chem Commun (Camb). 2002;(20):2372–3.

16. Trask A V, Motherwell WDS, Jones W. Solvent-drop
grinding: green polymorph control of cocrystallisation.
Chem Commun (Camb). 2004;(7):890–1.

17. Braga D, Grepioni F. Making crystals from crystals: a
green route to crystal engineering and polymorphism.
Chem Commun (Camb). 2005;(29):3635–45.

18. Alkhamis K a, Obaidat A a, Nuseirat AF. Solid-state
characterization of fl uconazole. Pharm Dev Technol.

19. Robertson JM, Ubbelohde a. R. A new form of
resorcinol. I. Structure Determination by X-Rays. Proc
R Soc A Math Phys Eng Sci. 1938;167(928):122–35.

20. Sanphui P, Goud R, Nangia A BU. Fast dissolving
curcumin co-crystals. 2011;99–130.

21. Sharma SM, Vijayakumar V, Sikka SK, Chidambaram
R. High pressure phase transitions in organic solids
l :α→β transition in resorcinol. 1985;25(1):75–9.

22. Panini P, Chattopadhyay B, Werzer O, Geerts Y. Crystal
growth alignment of β-polymorph of resorcinol in
thermal gradient. Cryst Growth Des. 2018;18(5):2681–

23. Hacioǧlu F, Önal A. Determination of eprosartan
mesylate and hydrochlorothiazide in tablets by
derivative spectrophotometric and high-performance
liquid chromatographic methods. J Chromatogr Sci.
How to Cite
ALATAS, Fikri Alatas et al. Preparation and Characterization of Fluconazole- Resorcinol Co-crystal. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 18, n. 2, p. 177-183, oct. 2020. ISSN 2614-6495. Available at: <>. Date accessed: 16 apr. 2024. doi: