Author(s):
Venkatkrishna J, Preethi Sudheer, Prakruthi MB, Samikcha Rai
Email(s):
preethisudheer@gmail.com
DOI:
10.52711/0974-360X.2025.00834 
Address:
Venkatkrishna J1, Preethi Sudheer2*, Prakruthi MB3, Samikcha Rai3
1,3Krupanidhi College of Pharmacy, Bangalore, India.
2Nitte College of Pharmaceutical Sciences (Nitte Deemed to be University), Bangalore, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 12,
Year - 2025
ABSTRACT:
Rivaroxaban is an anticoagulant and factor Xa inhibitor that acts in deep vein thrombosis. The aim of this study was to prepare a mouth-disintegrating film for the drug to improve its clinical acceptance. As a Biopharmaceutics classification system (BCS) II candidate, the drug requires a significant improvement in solubility to be present as a film. An antisolvent addition method was employed to prepare the cocrystals using gallic acid as a coformer. The optimum nano-crystal formulation (via custom experimental design) was incorporated into a hydroxy propyl methyl cellulose (HPMC) film. The oral films were subjected to physical evaluation, drug content, disintegration time, and drug release studies. Saturation solubility of 0.149 - 1.83 mg/ml was observed. The in vitro release studies showed a drug release of 30±0.14% to 58.2±0.26% at 10min. 49.3±0.18 to 98.7±0.36% at 120min. The optimum formulation solubility and dissolution rate were 1.61mg/ml and 90 %±0.25 at 60min. The X-ray diffraction pattern of the optimum formulation indicated a change in the crystalline nature of rivaroxaban, and the DSC results supported this observation. Films disintegrated in 47s± 0.5 s, and a two-fold increase in drug release from the film (%) was observed in contrast to the pure drug. The nano-cocrystal-incorporated rivaroxaban oral film can be used to improve the therapeutic potential of the drug.
Cite this article:
Venkatkrishna J, Preethi Sudheer, Prakruthi MB, Samikcha Rai. An Investigation on Crystal Engineered Rivaroxaban in Developing Orodispersible film. Research Journal Pharmacy and Technology. 2025;18(12):5785-2. doi: 10.52711/0974-360X.2025.00834
Cite(Electronic):
Venkatkrishna J, Preethi Sudheer, Prakruthi MB, Samikcha Rai. An Investigation on Crystal Engineered Rivaroxaban in Developing Orodispersible film. Research Journal Pharmacy and Technology. 2025;18(12):5785-2. doi: 10.52711/0974-360X.2025.00834 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-12-24
REFERENCES:
1. Jog R, Burgess DJ. Pharmaceutical amorphous nanoparticles. J Pharm Sci. 2017; 106(1): 39–65. Available from: http://dx.doi.org/10.1016/j.xphs.2016.09.014
2. Choi J-S, Lee S-E, Jang WS, Byeon JC, Park J-S. Tadalafil solid dispersion formulations based on PVP/VA S-630: Improving oral bioavailability in rats. Eur J Pharm Sci. 2017; 106: 152–8. Available from: http://dx.doi.org/10.1016/j.ejps.2017.05.065
3. Jit T, Shil D, Kumari Dasgupta R, Mallick S, Mukherjee S. Cocrystal: A review on the design and preparation of pharmaceutical cocrystals. Asian J Res Pharm Sci. 2023; 296–302. Available from: http://dx.doi.org/10.52711/2231-5659.2023.00050
4. Doloking H, Syamsi Dhuha N, Nurjannah N. Formation, Characterization and In vitro Dissolution studies of Piroxicam-Malic Acid Cocrystals. Res J Pharm Technol. 2024; 3061–6. Available from: http://dx.doi.org/10.52711/0974-360x.2024.00479
5. Mureşan-Pop M, Chiriac LB, Martin F, Simon S. Novel nutraceutical Myricetin composite of enhanced dissolution obtained by co-crystallization with acetamide. Compos B Eng. 2016; 89: 60–6. Available from: http://dx.doi.org/10.1016/j.compositesb.2015.11.024
6. Karimi-Jafari M, Padrela L, Walker GM, Croker DM. Creating cocrystals: A review of pharmaceutical cocrystal preparation routes and applications. Cryst Growth Des. 2018; 18(10): 6370–87. Available from: http://dx.doi.org/10.1021/acs.cgd.8b00933
7. Lindhoff-Last E, Samama MM, Ortel TL, Weitz JI, Spiro TE. Assays for measuring rivaroxaban: Their suitability and limitations. Ther Drug Monit. 2010; 32(6): 673–9. Available from: http://dx.doi.org/10.1097/ftd.0b013e3181f2f264
8. Douxfils J, Mullier F, Loosen C, Chatelain C, Chatelain B, Dogné J-M. Assessment of the impact of rivaroxaban on coagulation assays: Laboratory recommendations for the monitoring of rivaroxaban and review of the literature. Thromb Res. 2012; 130(6): 956–66. Available from: http://dx.doi.org/10.1016/j.thromres.2012.09.004
9. Bratsos S. Pharmacokinetic properties of rivaroxaban in healthy human subjects. Cureus. 2019; Available from: http://dx.doi.org/10.7759/cureus.5484
10. Scarpa M, Paudel A, Kloprogge F, Hsiao WK, Bresciani M, Gaisford S, et al. Key acceptability attributes of orodispersible films. Eur J Pharm Biopharm. 2018; 125:131–40. Available from: http://dx.doi.org/10.1016/j.ejpb.2018.01.003
11. Saxena A, Tewari G, Saraf SA. Formulation and evaluation of mucoadhesive buccal patch of acyclovir utilizing inclusion phenomenon. Braz J Pharm Sci. 2011; 47(4): 887–97. Available from: http://dx.doi.org/10.1590/s1984-82502011000400026
12. Liew KB, Tan YTF, Peh KK. Characterization of oral disintegrating film containing donepezil for Alzheimer disease. AAPS PharmSciTech. 2012; 13(1): 134–42. Available from: http://dx.doi.org/10.1208/s12249-011-9729-4
13. Bhandari J, Kanswami N, Lakshmi PK L. Nano Co-crystal Engineering Technique to Enhance the Solubility of Ezetimibe. J Young Pharm. 2020; 12: s10–s15.
14. S. Gurav A, S. Kulkarni A. Efavirenz cocrystals with Ascorbic acid: A Strategy for Polymorphic Modification and improvement of Dissolution properties. Res J Pharm Technol. 2024; 213–21. Available from: http://dx.doi.org/10.52711/0974-360x.2024.00034
15. Thakor P, Yadav B, Modani S, Shastri NR. Preparation and optimization of nano-sized cocrystals using a quality by design approach. CrystEngComm. 2020; 22(13): 2304–14. Available from: http://dx.doi.org/10.1039/c9ce01930h
16. Nandi S, Das G, Hussan Reza K. Formulation, evaluation and optimization of orally disintegrating films of Azithromycin using DOE approach for the pediatrics with acute otitis media. Res J Pharm Technol. 2022; 5031–7. Available from: http://dx.doi.org/10.52711/0974-360x.2022.00846
17. Liew KB, Tan YTF, Peh KK. Characterization of oral disintegrating film containing donepezil for Alzheimer disease. AAPS PharmSciTech. 2012; 13(1): 134–42. Available from: http://dx.doi.org/10.1208/s12249-011-9729-4
18. Shewale S, Shete AS, Doijad RC, Kadam SS, Patil VA, Yadav AV. Formulation and solid state characterization of nicotinamide-based co-crystals of fenofibrate. Indian J Pharm Sci. 2015; 77(3): 328. Available from: http://dx.doi.org/10.4103/0250-474x.159669
19. Xue X, Cao M, Ren L, Qian Y, Chen G. Preparation and optimization of rivaroxaban by self-nanoemulsifying drug delivery system (SNEDDS) for enhanced oral bioavailability and no food effect. AAPS PharmSciTech [Internet]. 2018; 19(4): 1847–59. Available from: http://dx.doi.org/10.1208/s12249-018-0991-6
20. Pi J, Wang S, Li W, Kebebe D, Zhang Y, Zhang B, et al. A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein. Asian J Pharm Sci 2019;14(2):154–64. Available from: http://dx.doi.org/10.1016/j.ajps.2018.04.009
21. Muddukrishna B.S. Krishnamurthy Bhat, Gautham G. Shenoy. Preparation and Solid State Characterization of Paclitaxel Cocrystals. Research J. Pharm. and Tech. 2014; 7(1): 64-69.
22. Elsayad MK, Mowafy HA, Zaky AA, Samy AM. Chitosan caged liposomes for improving oral bioavailability of rivaroxaban: in vitro and in vivo evaluation. Pharm Dev Technol. 2021; 26(3): 316–27. Available from: http://dx.doi.org/10.1080/10837450.2020.1870237
23. Thimmasetty, Nn S, Raheem T A, Skk S, Tanmoy. Modafinil cocrystals for altered physicochemical properties. Res J Pharm Technol. 2021; 4891–6. Available from: http://dx.doi.org/10.52711/0974-360x.2021.00850
24. Demir H, Gulsun T, Ozkan MH, Nemutlu E, Sahin S, Öner L. Assessment of dose proportionality of rivaroxaban nanocrystals. AAPS PharmSciTech. 2020; 21(6). Available from: http://dx.doi.org/10.1208/s12249-020-01776-z
25. Nirmala D, Nandhini S, Sudhakar M. Design and evaluation of fast dissolving oral films of Zolpidem by solvent casting method. Asian J Pharm Res. 2016; 6(2): 67. Available from: http://dx.doi.org/10.5958/2231-5691.2016.00012.5
26. Chonkar AD, Bhagawati ST, Udupa N. An overview on fast dissolving oral films. Asian J Pharm Technol. 2015; 5(3): 129. Available from: http://dx.doi.org/10.5958/2231-5713.2015.00020.3
27. Venkata Krishna J, Sudheer P. Advancement in the therapeutic potential of drug candidates via oral films: a brief update. J Res Pharm]. 2023; 27(2)(27(2)): 595–608. Available from: http://dx.doi.org/10.29228/jrp.342
28. Al-Mogherah AI, Ibrahim MA, Hassan MA. Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films. Saudi Pharm J. 2020; 28(11): 1374–82. Available from: http://dx.doi.org/10.1016/j.jsps.2020.09.001
29. Vyas Murthy A, Usha Ayalasomayajula L, Rani Earle R, Jyotsna P. Formulation and Evaluation of Tramadol Hydrochloride Oral Thin Films. Int J Pharma Sci Res. 2018; 9(4): 1692.
30. Srinivas A, Bhikshapathi DVRN. Fast Dissolving Oral Films of Pramipexole HCl monohydrate: Preparation and in vitro evaluation. Res J Pharm Technol. 2018; 11(3): 1001. Available from: http://dx.doi.org/10.5958/0974-360x.2018.00187.7
31. Keerthi Sai K. Formulation Development and In vitro Evaluation of Memantine Hydrochloride Fast Dissolving Oral Films employing different grades of Hydroxy Propyl Methyl Cellulose. Res J Pharm Technol. 2022; 17–23. Available from: http://dx.doi.org/10.52711/0974-360x.2022.00004
32. Chonkar AD, Bhagawati ST, Udupa N. An Overview on Fast Dissolving Oral Films. Asian J Pharm Technol. 2015; 5: 129.
33. Lou H, Liu M, Qu W, Hu Z, Brunson E, Johnson J, et al. Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics. Drug Dev Ind Pharm. 2014; 40(7): 910–8. Available from: http://dx.doi.org/10.3109/03639045.2013.789907
34. Celebier M, Kaynak MS, Altinoz S, Sahin S. UV spectrophotometric method for determination of the dissolution profile of rivaroxaban. Dissolution Technol. 2014; 21(4): 56–9. Available from: http://dx.doi.org/10.14227/dt210414p56