“DEVELOPMENT AND OPTIMIZATION OF DANAZOL CO-CRYSTAL LOADED TABLET TO TREAT ENDOMETRIOSIS”

Vidya Patil; Shivraj Jadhav; Sunil Mahajan

doi:10.56782/pps.525

Published : 2025-10-01

No. 2025 (Early Access)

“DEVELOPMENT AND OPTIMIZATION OF DANAZOL CO-CRYSTAL LOADED TABLET TO TREAT ENDOMETRIOSIS”

Vidya Patil

Shivraj Jadhav

Sunil Mahajan

DOI: https://doi.org/10.56782/pps.525

Abstract

This study aimed to develop, optimize, and characterize Danazol co-crystal-loaded tablets to enhance solubility and dissolution, thereby improving therapeutic efficacy in the treatment of endometriosis. Danazol co-crystals were prepared using various pharmaceutically acceptable co-formers via the solvent evaporation method and characterized using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Among the systems studied, Danazol-malonic acid co-crystals (1:2 molar ratio) demonstrated the greatest solubility enhancement (11.42 ± 0.53 μg/mL), corresponding to a 13.76-fold increase compared to pure Danazol. The formation of a novel crystalline phase was confirmed by distinct XRD peaks at 2θ values of 19° and 21°. Co-crystals were incorporated into tablets using direct compression and optimized using a 3² factorial design, with sodium croscarmellose (8–24 mg) and polyvinylpyrrolidone K-30 (4–20 mg) as independent variables. The formulations were assessed for pre-compression characteristics, tablet quality parameters, disintegration time, in vitro drug release, and stability. Statistical analysis revealed strong predictive models for disintegration time (R² = 0.9971) and drug release (R² = 0.9483). The optimized formulation (VF7) containing 24 mg sodium croscarmellose and 4 mg PVP K-30 exhibited rapid disintegration (74.0 ± 3.2 s) and significantly improved dissolution (95.8 ± 2.0% at 60 min), outperforming the marketed formulation (75.2 ± 2.7%). The optimized tablets remained stable under accelerated conditions (40°C/75% RH) for three months. These findings highlight the potential of co-crystallization and formulation optimization to overcome solubility challenges, offering a promising strategy for improving the clinical performance of Danazol in endometriosis therapy.

Keywords:

Keywords: Danazol, Co – Crystallization, Solubility, enhancement, Factorial Design etc.

Similar Articles

Rama Devi Korni, Thanmaisree Bora, Akhil Majji, Jagadeesh Panda, Liquisolid technique for solubility enhancement of a poorly soluble thrombin inhibitor: optimization using design of experiments and artificial neural networks , Prospects in Pharmaceutical Sciences: Vol. 23 No. 3 (2025)
Dr. Ashwini Madgulkar, Dr. Mangesh Bhalekar, Abhishek Kunjir, Maryam Mulla, A SCIENTIFIC EXPLORATION OF CO-AMORPHOUS FORMULATION DRIVEN BY KNOWLEDGE BASED VIRTUAL SCREENING FOR SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT OF DARUNAVIR , Prospects in Pharmaceutical Sciences: No. 2025 (Early Access)
Vijayraj Sonawane, Dhanashree I. Wagh, Sakshi P. Bhamare, Khemchand R. Surana, Deepak D. Sonawane, Sunil K. Mahajan, ENHANCING WATER SOLUBILITY OF A BCS CLASS II DRUG USING HYDROTROPY, MIXED SOLVENCY, COSOLVENCY, AND NANOSUSPENSION TECHNIQUES , Prospects in Pharmaceutical Sciences: No. 2025 (Early Access)
Monika Nijhawan, Bhavana Jidige, Rajeswari Aleti, Sailaja Gunnam, Trapti Saxena, Development and characterization of voriconazole-oxalic acid dihydrate cocrystals for enhanced pharmaceutical performance , Prospects in Pharmaceutical Sciences: Vol. 22 No. 4 (2024)
Sailaja Gunnam, Sindhura T, Rajeswari Aleti, Monika Nijhawan, Bi-layer tablets of sitagliptin phosphate & metformin hydrochloride – preparation and evaluation , Prospects in Pharmaceutical Sciences: Vol. 23 No. 3 (2025)
monika nijhawan, Rajeswari Aleti, Sravani Maramwar, Dedipya Goda Srivalli Vangala, Trapti Saxena, Solubility Enhancement of Diacerein Through Liquisolid Technology: A Formulation Perspective , Prospects in Pharmaceutical Sciences: No. 2025 (Early Access)
Ewa Napiórkowska, Overview of cyclodextrins and medicinal products containing cyclodextrins currently registered in Poland , Prospects in Pharmaceutical Sciences: Vol. 21 No. 3 (2023)
Rushikesh Mahale, Shivraj Jadhav, Sunil Mahajan, Development and optimization of gastro retentive floating tablets of dapsone for controlled release , Prospects in Pharmaceutical Sciences: No. 2025 (Early Access)
Priya Jagtap, Dr. Reshma Jadhav, Dr. Ashish Jain, Bhavesh Mahajan, Prapti Gawand, Prathamesh Chaudhari, Aishwarya Patil, Quality by design approach in HPLC method development and validation for simultaneous determination of abiraterone acetate and prednisolone with greenness assessment , Prospects in Pharmaceutical Sciences: Vol. 23 No. 3 (2025)
Bartłomiej Pyrak, Tomasz Gubica, Karolina Rogacka-Pyrak, Cyclodextrin nanosponges as bioenhancers of phytochemicals , Prospects in Pharmaceutical Sciences: Vol. 22 No. 3 (2024)

1 2 3 4 > >>

You may also start an advanced similarity search for this article.

Details

References

Statistics

Authors

Download files

PDF

Citation rules

Patil, V., Jadhav, S., & Mahajan, S. (2025). “DEVELOPMENT AND OPTIMIZATION OF DANAZOL CO-CRYSTAL LOADED TABLET TO TREAT ENDOMETRIOSIS”. Prospects in Pharmaceutical Sciences, (2025 (Early Access). https://doi.org/10.56782/pps.525

Altmetric indicators

Cited by / Share

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License.

References

1. M. Horan, Fertility Preservation in Young Women at Risk of Ovarian Insufficiency due to Malignancy or Endometriosis, Ph.D. dissertation, School of Medicine, University College Dublin, 2022.

2. S. A. Missmer et al., “Impact of Endometriosis on Life-Course Potential: A Narrative Review,” Int. J. Gen. Med., vol. 14, pp. 9–25, 2021, doi: 10.2147/IJGM.S261139.

3. G. Bonavina and H. S. Taylor, “Endometriosis-associated infertility: From pathophysiology to tailored treatment,” Front. Endocrinol., vol. 13, p. 1020827, 2022.

4. S. A. Missmer et al., “Impact of Endometriosis on Life-Course Potential: A Narrative Review,” Int. J. Gen. Med., vol. 14, pp. 9–25, 2021, doi: 10.2147/IJGM.S261139.

5. A. A. Ekine, “Effects of Endometriosis on Quality of Life (Benefit of combined hystero-laparoscopic surgery on quality of life and fertility performance in endometriosis),” 2025.

6. J. Donnez, L. Cacciottola, J.-L. Squifflet, and M.-M. Dolmans, “Profile of Linzagolix in the Management of Endometriosis, Including Design, Development and Potential Place in Therapy: A Narrative Review,” Drug Des. Devel. Ther., vol. 17, pp. 369–380, 2023, doi: 10.2147/DDDT.S269976.

7. J. S. Fuqua and E. A. Eugster, “History of puberty: normal and precocious,” Horm. Res. Paediatr., vol. 95, pp. 568–578, 2022.

8. M. D. Gonçalves et al., “Recent Advances in Biotransformation by Cunninghamella Species,” Curr. Drug Metab., vol. 22, pp. 1035–1064, 2021, doi: 10.2174/1389200222666211126100023.

9. A. A. Al-Badr, “Chapter Five - Danazol,” in Profiles of Drug Substances, Excipients and Related Methodology, vol. 47, A. A. Al-Majed, Ed. Academic Press, 2022, pp. 149–326, doi: 10.1016/bs.podrm.2021.10.005.

10. H.-E. Huang et al., “Danazol in Refractory Autoimmune Hemolytic Anemia or Immune Thrombocytopenia: A Case Series Report and Literature Review,” Pharmaceuticals, vol. 15, p. 1377, 2022, doi: 10.3390/ph15111377.

11. M. Riva et al., “Danazol Treatment for Thrombocytopenia in Myelodysplastic Syndromes: Can an ‘Old-fashioned’ Drug be Effective?” HemaSphere, vol. 7, p. e867, 2023, doi: 10.1097/HS9.0000000000000867.

12. I. Nyamba et al., “Pharmaceutical approaches for enhancing solubility and oral bioavailability of poorly soluble drugs,” Eur. J. Pharm. Biopharm., vol. 204, p. 114513, 2024, doi: 10.1016/j.ejpb.2024.114513.

13. G. Madhuri and R. Nagaraju, “An Overview on Novel Particle Engineering Designing: Co-crystallization Techniques,” Int. J. Pharm. Sci. Rev. Res., vol. 66, pp. 88–101, 2021, doi: 10.47583/ijpsrr.2021.v66i01.015.

14. H. Sami, N. Akhtar, A. Jain, and A. K. Singhai, “Co-Crystals in Pharmaceutical Science: An Updated Review,” 2023.

15. M. R. Dhondale et al., “Co-Crystallization Approach to Enhance the Stability of Moisture-

16. M. Bhatia, A. Kumar, V. Verma, and S. Devi, “Development of ketoprofen-p-aminobenzoic acid co-crystal: formulation, characterization, optimization, and evaluation,” Med. Chem. Res., vol. 30, pp. 2090–2102, 2021, doi: 10.1007/s00044-021-02794-7.

17. Y. Tatsumi, Y. Shimoyama, and S. G. Kazarian, “Analysis of the Dissolution Behavior of Theophylline and Its Cocrystal Using ATR-FTIR Spectroscopic Imaging,” Mol. Pharm., vol. 21, pp. 3233–3239, 2024, doi: 10.1021/acs.molpharmaceut.4c00002.

18. H. Zhang et al., “Novel Ascorbic Acid Co-Crystal Formulations for Improved Stability,” Molecules, vol. 27, p. 7998, 2022, doi: 10.3390/molecules27227998.

19. A. Chettri, A. Subba, G. P. Singh, and P. P. Bag, “Pharmaceutical co-crystals: A green way to enhance drug stability and solubility for improved therapeutic efficacy,” J. Pharm. Pharmacol., vol. 76, pp. 1–12, 2024, doi: 10.1093/jpp/rgad097.

20. S. S. Al-Nimry and M. S. Khanfar, “Enhancement of the Solubility of Asenapine Maleate Through the Preparation of Co-Crystals,” Curr. Drug Deliv., vol. 19, pp. 788–800, 2022, doi: 10.2174/1567201818666210805154345.

21. Z. Huang, S. Staufenbiel, and R. Bodmeier, “Combination of co-crystal and nanocrystal techniques to improve the solubility and dissolution rate of poorly soluble drugs,” Pharm. Res., vol. 39, pp. 949–961, 2022, doi: 10.1007/s11095-022-03243-9.

22. X. Ji et al., “Enhanced Solubility, Dissolution, and Permeability of Abacavir by Salt and Cocrystal Formation,” Cryst. Growth Des., vol. 22, pp. 428–440, 2022, doi: 10.1021/acs.cgd.1c01051.

23. T. V. H. H. Nadh, P. S. Kumar, M. V. Ramana, and N. R. Rao, “Formulation and Optimization of Zolmitriptan Orodispersible Tablets,” J. Drug Deliv. Ther., vol. 11, p. 50, 2021, doi: 10.22270/jddt.v11i3.4703.

24. Formulation and Evaluation of Pharmaceutical Co-Crystals,” Asian J. Res. Chem., vol. 14, no. 4, 2021. [Online]. Available

25. S. Jadhav, “Formulation of Tablet of Ivermectin Co-Crystal for Enhancement of Solubility and Other Physical Properties,” 2023. [Online]. Available: (accessed Feb. 28, 2025).

26. H. Abdelrahman, E. Essa, G. E. Maghraby, and M. Arafa, “L-proline as Co-crystal Forming Amino Acid for Enhanced Dissolution Rate of Lamotrigine: Development of Buccal Tablet,” Indones. J. Pharm., pp. 574–583, 2023, doi: 10.22146/ijp.6867.

27. T. Eidevåg, E. S. Thomson, D. Kallin, J. Casselgren, and A. Rasmuson, “Angle of repose of snow: An experimental study on cohesive properties,” Cold Reg. Sci. Technol., vol. 194, p. 103470, 2022, doi: 10.1016/j.coldregions.2021.103470.

28. Formulation and Evaluation of Some Cocrystals for Enhanced Drug Properties,” Res. J. Pharm. Technol., vol. 14, no. 3, 2021. [Online]. Available:

29. A. F. Al-Dulaimi, M. Al-kotaji, and F. T. Abachi, “Paracetamol/naproxen co-crystals; a simple way for improvement of flowability, tableting and dissolution properties,” 2021.

30. C. Botella-Martínez, M. Viuda-Martos, J. A. Fernández-López, J. A. Pérez-Alvarez, and J. Fernández-López, “Development of plant-based burgers using gelled emulsions as fat source and beetroot juice as colorant: Effects on chemical, physicochemical, appearance and sensory characteristics,” LWT, vol. 172, p. 114193, 2022, doi: 10.1016/j.lwt.2022.114193.

31. J. Simão, S. A. Chaudhary, and A. J. Ribeiro, “Implementation of Quality by Design (QbD) for development of bilayer tablets,” Eur. J. Pharm. Sci., vol. 184, p. 106412, 2023, doi: 10.1016/j.ejps.2023.106412.

32. M. Ficzere et al., “Real-time coating thickness measurement and defect recognition of film coated tablets with machine vision and deep learning,” Int. J. Pharm., vol. 623, p. 121957, 2022, doi: 10.1016/j.ijpharm.2022.121957.

33. M. Momeni, M. Afkanpour, S. Rakhshani, A. Mehrabian, and H. Tabesh, “A prediction model based on artificial intelligence techniques for disintegration time and hardness of fast disintegrating tablets in pre-formulation tests,” BMC Med. Inform. Decis. Mak., vol. 24, p. 88, 2024, doi: 10.1186/s12911-024-02485-4.

34. H. Zhao et al., “A new parameter for characterization of tablet friability based on a systematical study of five excipients,” Int. J. Pharm., vol. 611, p. 121339, 2022, doi: 10.1016/j.ijpharm.2021.121339.

35. A. Berardi et al., “Advancing the understanding of the tablet disintegration phenomenon – An update on recent studies,” Int. J. Pharm., vol. 598, p. 120390, 2021, doi: 10.1016/j.ijpharm.2021.120390.

36. A. Farquharson et al., “Drug Content Uniformity: Quantifying Loratadine in Tablets Using a Created Raman Excipient Spectrum,” Pharmaceutics, vol. 13, p. 309, 2021, doi: 10.3390/pharmaceutics13030309.

37. S. Chakraborty and D. S. Mondal, “A Green Eco-friendly Analytical Method Development, Validation, and Stress Degradation Studies of Favipiravir in Bulk and Different Tablet Dosages Form by UV-spectrophotometric and RP-HPLC Methods with their Comparison by Using ANOVA and in-vitro Dissolution Studies,” Int. J. Pharm. Investig., vol. 13, pp. 290–305, 2023, doi: 10.5530/ijpi.13.2.039.

38. O. González-González et al., “Drug Stability: ICH versus Accelerated Predictive Stability Studies,” Pharmaceutics, vol. 14, p. 2324, 2022, doi: 10.3390/pharmaceutics14112324.

39. S. Parvarinezhad, M. Salehi, M. Kubicki, and R. E. Malekshah, “Synthesis, characterization, spectral studies and evaluation of noncovalent interactions in co-crystal of μ-oxobridged polymeric copper(II) complex derived from pyrazolone by theoretical studies,” J. Mol. Struct., vol. 1260, p. 132780, 2022, doi: 10.1016/j.molstruc.2022.132780.

40. B. Rojek, A. Bartyzel, E. Leyk, and A. Plenis, “Arbidol hydrochloride compatibility study with starchy excipients using DSC, FTIR, TGA-FTIR, and PXRD methods,” J. Therm. Anal. Calorim., 2025, doi: 10.1007/s10973-025-14056-4.

41. M. Bhatia and S. Devi, “Co-crystallization: a green approach for the solubility enhancement of poorly soluble drugs,” CrystEngComm, vol. 26, pp. 293–311, 2024, doi: 10.1039/D3CE01047C.

42. J. Han et al., “Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System,” Pharmaceutics, vol. 13, p. 1725, 2021, doi: 10.3390/pharmaceutics13101725.

43. J. C. Adama, C. G. Arocha, and P. O. Ogbobe, “Determination of some physical properties, angles of repose and frictional properties of a local variety of kernel and nut of oil palm,” Niger. J. Technol., vol. 41, pp. 365–369, 2022, doi: 10.4314/njt.v41i2.18.

44. S. Kole, R. Vinchurkar, A. Gawade, and A. Kuchekar, “The Impact of Co-crystal Formation on the Stability of Camylofin Dihydrochloride Immediate Release Tablets,” Hacet. Univ. J. Fac. Pharm., vol. 44, pp. 108–123, 2024, doi: 10.52794/hujpharm.1331991.

45. R. Iovanov et al., “Testing the disintegration and texture-related palatability predictions for orodispersible tablets using an instrumental tool coupled with multivariate analysis: Focus on process variables and analysis settings,” Eur. J. Pharm. Sci., vol. 198, p. 106801, 2024, doi: 10.1016/j.ejps.2024.106801.

46. S. Devi et al., “Ketoprofen–FA Co-crystal: In Vitro and In Vivo Investigation for the Solubility Enhancement of Drug by Design of Expert,” AAPS PharmSciTech, vol. 23, p. 101, 2022, doi: 10.1208/s12249-022-02253-5.

47. B. Zarrik et al., “Adsorption of crystal violet using a composite based on graphene Oxide-ED@Cellulose: Adsorption modeling, optimization and recycling,” Inorg. Chem. Commun., vol. 162, p. 112179, 2024, doi: 10.1016/j.inoche.2024.112179.

48. S. Mazloomi et al., “Parametric study and process modeling for metronidazole removal by rhombic dodecahedron ZIF-67 crystals,” Sci. Rep., vol. 13, p. 14654, 2023, doi: 10.1038/s41598-023-41724-y.

49. S. Ruhil, M. Dahiya, H. Kaur, and J. Singh, “New insights into the disintegration mechanism and disintegration profiling of rapidly disintegrating tablets (RDTs) by thermal imaging,” Int. J. Pharm., vol. 611, p. 121283, 2022, doi: 10.1016/j.ijpharm.2021.121283.

50. C. Hu, F. Zhang, and H. Fan, “Evaluation of Drug Dissolution Rate in Co-amorphous and Co-crystal Binary Drug Delivery Systems by Thermodynamic and Kinetic Methods,” AAPS PharmSciTech, vol. 22, p. 21, 2021, doi: 10.1208/s12249-020-01864-0.

51. I. Janilkarn-Urena et al., “Improving the solubility of pseudo-hydrophobic chemicals through co-crystal formulation,” PNAS Nexus, vol. 4, p. pgaf007, 2025, doi: 10.1093/pnasnexus/pgaf007.

52. L. Orszulak et al., “Inhibition of naproxen crystallization by polymers: The role of topology and chain length of polyvinylpyrrolidone macromolecules,” Eur. J. Pharm. Biopharm., vol. 207, p. 114581, 2025, doi: 10.1016/j.ejpb.2024.114581.

53. B. Priya et al., “Temozolomide cocrystal forms with enhanced dissolution, stability and biological activity towards Glioblastoma,” J. Mol. Struct., vol. 1313, p. 138751, 2024, doi: 10.1016/j.molstruc.2024.138751.

Vidya Patil

vidyapatil03112001@gmail.com

Affiliation:

a:1:{s:5:"en_US";s:35:"Divine College of Pharmacy, Satana ";} India

“DEVELOPMENT AND OPTIMIZATION OF DANAZOL CO-CRYSTAL LOADED TABLET TO TREAT ENDOMETRIOSIS”

Vidya Patil

Shivraj Jadhav

Sunil Mahajan

Abstract

Keywords:

Most read articles by the same author(s)

Similar Articles

Vidya Patil

Shivraj Jadhav

Sunil Mahajan