Preparation and Characterization Studies of Nanofiber and Orodispersable Film Formulations of Enoxolone

Year 2022, Volume: 26 Issue: 5, 1242 - 1251, 28.06.2025

Juste Baranauskaıte Ortasöz , Burcu Üner

Abstract

Enoxolone is a pentacyclic triterpenoid observed from Glycyrrhiza glabra and it has an
antibacterial, antiviral and antifungal effects. However, enoxolone (ENX) has low oral bioavailability due
to a first pass metabolism effect in the intestinal tract, poor intestinal permeability. The aim of this study
was to develop the PVP based orodispersible films (ODFs) containing ENX by electrospinning and solvent
casting methods and to compare in terms of their credibility for orodispersible delivery of ENX through a
variety of in vitro and physical investigations. Physical properties such as thichness, weight variation, tensile
strength, Young's modulus and elongation at break were investigated. Moreover, the in vitro release profile
of ENX from prepared films were characterized in this study. The morphological structures of the prepared
film formulations were examined under scanning electron microscope and the interaction between the ENX,
film and PVP were determined by the FTIR spectroscopy.DSC analysis was performed to understand the
thermal behavior of formulations and components. The results obtained proved that the electrospinning
process can be used to produce ODF formulations with lower disintegration time (≈4.52 min), lower
diameter (≈218.5 nm) and acceptable mechanical strength (≈370.55 MPa). The preliminary results as a proofof-
concept demonstration reported here will shed a new light on the future design and application of ODFs
by electrospinning method.

Keywords

nanofiber , enoxolone , edible film , electrospinning

References

• [1] Wu YH, Yu DG, Li JJ, Wang Q, Li HP, Li XY. Medicated multiple-component polymeric nanocomposites fabricated using electrospraying. Polym Polym Compos. 2017; 25, 57-62. [CrossRef]
• [2] Xie SR, Zhao J, Liu R. Study and expectation of glycyrrhetic acid. J Dalian Univ. 2005; 26: 84-86. [CrossRef]
• [3] Jin M, Wu HJ. Advancement on pharmacological action of glycyrrhetic acid. Med Recapitulate. 2009; 15: 1712–1715. [CrossRef]
• [4] Salari MH, Sohrabi N, Kadkhoda Z, Khalili MB. Antibacterial effects of enoxolone on periodontopathogenic and capnophilic bacteria isolated from specimens of periodontitis patients. Iran Biomed J. 2003; 7: 39-42. [CrossRef]
• [5] Jin L, Dai L, Ji M, Wang H. Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs. Bioorg Chem. 2019; 85: 179-190. [CrossRef]
• [6] Alexander A, Patel RJ, Saraf S, Saraf S. Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. J Control Release. 2016; 241: 110–124. [CrossRef]
• [7] Homayun B, Lin X, Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics. 2019; 11: 1-29. [CrossRef]
• [8] Jani R, Patel D. Hot melt extrusion: An industrially feasible approach for casting orodispersible film. Asian J Pharm Sci. 2015; 10: 292-305. [CrossRef]
• [9] Ghosal K, Chandra A, Roy S, Agatemor C, Thomas S, Provaznik I. Electrospinning over solvent casting: tuning of mechanical properties of membranes. Sci Rep. 2018; 8: 1-9. [CrossRef]
• [10] Tian Y, Orlu M, Woerdenbag HJ, Scarpa M, Kiefer O, Kottke D, Sjöholm E, Öblom H, Sandler N, Hinrichs WLJ. Oromucosal films: From patient centricity to production by printing techniques. Expert Opin Drug Deliv. 2019; 16: 981–993. [CrossRef]
• [11] Chachlioutaki K, Tzimtzimis EK, Tzetzis D, Chang MW, Ahmad Z, Karavasili C, Fatouros DG. Electrospun Orodispersible Films of Isoniazid for Pediatric Tuberculosis Treatment. Pharmaceutics. 2020; 12: 1-14. [CrossRef]
• [12] Zhang H, Niu Q, Wang N, Nie J, Ma G. Thermo-sensitive drug controlled release PLA core/PNIPAM shell fibers fabricated using a combination of electrospinning and UV photo-polymerization. Eur Polym J. 2015; 71: 440–450. [CrossRef]
• [13] Li C, Yu DG, Williams GR, Wang ZH. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process. PLoS ONE. 2014; 9: 1-9. [CrossRef]
• [14] Vongsetskul T, Wongsomboon TCP, Rangkupan R. Effect of solvent and processing parameters on electrospun polyvinylpyrrolidone ultra-fine fibers. Chiang Mai J Sci. 2015; 42: 436-442. [CrossRef]
• [15] Preis M, Pein M, Breitkreutz J. Development of a taste-masked orodispersible film containing dimenhydrinate. Pharmaceutics. 2012; 4(4): 551-562. [CrossRef]
• [16] Takeuchi Y, Umemura K, Tahara K, Takeuchi H. Formulation design of hydroxypropyl cellulose films for use as orally disintegrating dosage forms. J Drug Deliv Sci Technol. 2018; 46: 93-100. [CrossRef]
• [17] Molla S, Compan V. Polyvinyl alcohol nanofiber reinforced Nafion membranes for fuel cell applications. J Membr Sci. 2011; 372(1-2): 191-200. [CrossRef]
• [18] Zhao K, Wang W, Teng A, Zhang K, Ma Y, Duan S, Guo Y. Using cellulose nanofibers to reinforce polysaccharide films: Blending vs layer-by-layer casting. Carbohydr Polym. 2020; 227: 1-9. [CrossRef]
• [19] Mushtaque M, Muhammad IN, Hassan SMF, Ali A, Masood R. Development and pharmaceutical evaluation of oral fast dissolving thin film of escitalopram: A patient friendly dosage form. Pak J Pharm Sci. 2020; 33(1): 183-189. [CrossRef]
• [20] Yu DG, Branford-White C, White K. Dissolution Improvement of Electrospun Nanofiber-Based Solid Dispersions for Acetaminophen. AAPS PharmSciTech. 2010; 11: 809–817. [CrossRef]
• [21] Nagaraju T, Gowthami R, Rajashekar M, Sandeep S, Mallesham M, Sathish D, Shravan Kumar Y. Comprehensive review on oral disintegrating films. Curr Drug Deliv. 2013; 10(1): 96-108. [CrossRef]
• [22] Garsuch V, Breitkreutz J. Comparative investigations on different polymers for the preparation of fast-dissolving oral films. J Pharm Pharmacol. 2010; 62(4): 539-545. [CrossRef]
• [23] Tong Y, Jiang Z, Wang C, Xin Y, Huang Z, Liu S, Li C. Effect of annealing on the morphology and properties of ZnS: Mn nanoparticles/PVP nanofibers. Mater Lett. 2008; 62(19): 3385-3387. [CrossRef]
• [24] Chamakh M, Ayesh AI. Production and investigation of flexible nanofibers of sPEEK/PVP loaded with RuO2 nanoparticles. Mater Des. 2021; 204: 1-8. [CrossRef]
• [25] Yang B, Wang L, Zhang M, Luo J, Ding X. Timesaving, high-efficiency approaches to fabricate aramid nanofibers. ACS nano. 2019; 13(7): 7886-7897. [CrossRef]
• [26] Galdeano MC, Mali S, Grossmann MVE, Yamashita F, García MA. Effects of plasticizers on the properties of oat starch films. Mater Sci Eng C. 2009; 29(2): 532-538. [CrossRef]
• [27] Dong L, Mai Y, Liu Q, Zhang W, Yang J. Mechanism and improved dissolution of glycyrrhetinic acid solid dispersion by alkalizers. Pharmaceutics. 2020; 12(1): 1-24. [CrossRef]
• [28] Ma X, Qiao C, Wang X, Yao J, Xu J. Structural characterization and properties of polyols plasticized chitosan films. Int. J Biol Macromol. 2019; 135: 240-245. [CrossRef]
• [29] He X, Yu S, Dong Y. Preparation and properties of a novel thermo-responsive poly(N-isopropylacrylamide) hydrogel containing glycyrrhetinic acid. J Mater Sci. 2009; 44: 4078–4086. [CrossRef]
• [30] Zhang C, Liu Z, Zheng Y, Geng Y, Han C, Shi Y, Kong L. Glycyrrhetinic acid functionalized graphene oxide for mitochondria targeting and cancer treatment in vivo. Small. 2018; 14(4): 1-16. [CrossRef]
• [31] Ren HM, Cai C, Leng CB, Pang SF, Zhang YH. Nucleation Kinetics in Mixed NaNO3/Glycerol Droplets Investigated with the FTIR–ATR Technique. J Phys Chem. 2016; 120(11): 2913-2920. [CrossRef]
• [32] Striugas N, Skvorčinskienė R, Paulauskas R, Zakarauskas K, Vorotinskienė L. Evaluation of straw with absorbed glycerol thermal degradation during pyrolysis and combustion by TG-FTIR and TG-GC/MS. Fuel. 2017; 204: 227- 235. [CrossRef]
• [33] Borodko Y, Habas SE, Koebel M, Yang P, Frei H, Somorjai GA. Probing the Interaction of Poly (vinylpyrrolidone) with Platinum Nanocrystals by UV− Raman and FTIR. J Phys Chem. 2006; 110(46): 23052-23059. [CrossRef]
• [34] Abdelghany AM, Mekhail MS, Abdelrazek EM, Aboud MM. Combined DFT/FTIR structural studies of monodispersed PVP/Gold and silver nano particles. J Alloys Compd. 2015; 646: 326-332. [CrossRef]
• [35] Celebioglu A, Uyar T. Metronidazole/Hydroxypropyl-β-Cyclodextrin inclusion complex nanofibrous webs as fastdissolving oral drug delivery system. Int J Pharm. 2019; 572: 1-36. [CrossRef]
• [36] Baranauskaite J, Adomavičiūtė E, Jankauskaitė V, Marksa M, Barsteigienė Z, Bernatoniene J. Formation and investigation of electrospun Eudragit E100/oregano mats. Molecules. 2019; 24: 1-13. [CrossRef]