Design optimization and evaluatıon of polyvinyl alcohol based oral thin film of apixaban

Year 2025, Volume: 29 Issue: 1, 123 - 136

Dr. Abhishek Kanugo

Abstract

The current research work aimed to prepare an optimized and evaluate fast-dissolving oral thin film of Apixaban using polyvinyl alcohol as a film former. The oral thin film of Apixaban enhances the solubility, bioavailability, and therapeutic efficacy in thrombus, pulmonary embolism, and venous thromboembolism. The chemical compatibility and thermal analysis were investigated with the help of FTIR, and DSC. The optimization was performed with the Box-Behnken design. The concentrations of film former (PVA: X1), plasticizer (PEG 200: X2), and superdisintegrant (cross povidone: X3) were considered as independent factors and the critical quality attributes for the oral films are disintegration time, dissolution, and folding endurance. The ANOVA comprised of Quadratic model which predicted p-values of 0.0039, 0.0105, and 0.0020 significant. The scanning electron microscopy assessed the texture of the film. An optimized batch P6 disintegrated within 19 seconds, released the drug (99.07 %) within 10 min and had a folding endurance of 116. The results conclude that optimized batch P6 of oral thin film of Apixaban significantly minimizes the deep vein thrombosis, pulmonary embolism, and venous thromboembolism due to fastest onset of action and improved solubility. Thus, the complications associated with the clotting of blood is sharply reduces.

Keywords

Oral thin film, Apixaban, Polyvinyl alcohol, Deep vein thrombosis, Box-Behnken design

References

• [1] Couti N, Porfire A, Lovanov R, Crian AG, Lurian S, Casian T, Tomuta L. Polyvinyl alcohol, a versatile excipient for pharmaceutical 3D printing. Polymers. 2024; 16(4): 517. https://doi.org/10.3390/polym16040517.
• [2] Gaaz TS, Sulong AB, Akhtar MN, Kadhum AAH, Mohamad AB, Al-Amiery AA. Properties and applications of polyvinyl alcohol, halloysite nanotubes and their nanocomposites. Molecules. 2015; 20(12):22833-22847. https://doi.org/10.3390/MOLECULES201219884.
• [3] Liu B, Zhang J, Guo H, Liu B, Zhang J, Guo H. Research progress of polyvinyl alcohol water-resistant film materials. Membranes. 2022;12(3):347. https://doi.org/10.3390/MEMBRANES12030347.
• [4] Oun AA, Shin GH, Rhim JW, Kim JT. Recent advances in polyvinyl alcohol-based composite films and their applications in food packaging. Food Packag Shelf Life. 2022; 34:100991. https://doi.org/10.1016/J.FPSL.2022.100991.
• [5] Kanugo A, Misra A. New and novel approaches for enhancing the oral absorption and bioavailability of protein and peptides therapeutics. Ther Deliv. 2020; 11; 713–732. https://doi.org/10.4155/tde-2020-0068.
• [6] Gupta MS, Kumar TP, Gowda DV, Rosenholm JM. Orodispersible films: Conception to quality by design. Adv Drug Deliv Rev. 2021;178:113983. https://doi.org/10.1.016/J.ADDR.2021.113983
• [7] Mayoclinic. Deep vein thrombosis (DVT) - Symptoms & causes - Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/deep-vein-thrombosis/symptoms-causes/syc-20352557. [Access Sepember 24, 2023].
• [8] Navarrete S, Solar C, Tapia R, Pereira J, Fuentes E, Palomo I. Pathophysiology of deep vein thrombosis. Clin Exp Med. 2023;23(3):645–654. https://doi.org/10.1007/S10238-022-00829-W.
• [9] Drugbank. Apixaban: Uses, Interactions, Mechanism of Action | DrugBank Online. https://go.drugbank.com/drugs/DB06605. [AccessAugust 5, 2023].
• [10] Terada R, Johnson PM, Butt AL, Mishima Y, Stewart KE, Levy JH, Tanaka KA. In vitro effects of Gla-domainless factor Xa analog on procoagulant and fibrinolytic pathways in apixaban-treated plasma and whole blood. Thromb Res. 2023;230:119–125. https://doi.org/10.1016/J.THROMRES.2023.08.018.
• [11] Tapre DN, Borikar SP, Jain SP, Walde SR, Tapadiya GG, Gurumukhi VC. Development and evaluation of novel famotidine-loaded fast dissolving sublingual film using the quality-by-design approach. J Drug Deliv Sci Technol. 2023;85:104581. https://doi.org/10.1016/J.JDDST.2023.104581.
• [12] Alaei S, Omidi Y, Omidian H. In vitro evaluation of adhesion and mechanical properties of oral thin films. Eur J Pharm Sci. 2021;166:105965. https://doi.org/10.1016/j.ejps.2021.105965.
• [13] Dugad T, Kanugo A. Design optimization and evaluation of solid lipid nanoparticles of azelnidipine for the treatment of hypertension. Recent Pat Nanotechnol. 2022;18(1):22–32. https://doi.org/10.2174/1872210517666221019102543.
• [14] Kanugo A, Gandhi Y. Formulation optimization and evaluation of oral thin film of bilastine for the treatment of allergic conditions. J Res Pharm. 2022;26(5):1214–1229. https://doi.org/10.29228/jrp.214.
• [15] Sevinç ÖR, Özakar E. Current overview of oral thin films. Turk J Pharm Sci. 2021;18(1):111. https://doi.org/10.4274/TJPS.GALENOS.2020.76390.
• [16] Khadra I, Obeid MA, Dunn C, Watts S, Halbert G, Ford S, Mullen A. Characterisation and optimisation of diclofenac sodium orodispersible thin film formulation. Int J Pharm. 2019;561:43–46. https://doi.org/10.1016/J.IJPHARM.2019.01.064.
• [17] Nair AB, Shah J, Jacob S, Al-Dhubiab BE, Patel V, Sreeharsha N, Shinu P. Development of Mucoadhesive buccal film for rizatriptan: In vitro and ın vivo evaluation. Pharmaceutics. 2021;13(5): 728. https://doi.org/10.3390/PHARMACEUTICS13050728.
• [18] Suthar C, Kanugo A. Liquisolid compact technique for the enhancement of solubility and dissolution rate of ambrisentan: Quality by design approach. Indian J Pharm Sci. 2022;84(6):1417–1428. https://doi.org/10.36468/pharmaceutical-sciences.1040.
• [19] Abdelhameed AH, Abdelhafez WA, Saleh kh I, Hamad AA, Mohamed MS. Formulation and optimization of oral fast dissolving films loaded with nanosuspension to enhance the oral bioavailability of Fexofenadine HCL. J Drug Deliv Sci Technol. 2023;85:104578. https://doi.org/10.1016/J.JDDST.2023.104578.
• [20] AnjiReddy K, Karpagam S. Hyperbranched cellulose polyester of oral thin film and nanofiber for rapid release of donepezil; preparation and in vivo evaluation. Int J Biol Macromol. 2019;124:871–887. https://doi.org/10.1016/j.ijbiomac.2018.11.224.
• [21] Gupta S, Kumar TP, Gowda DV. Patent perspective on orodispersible films. Recent Pat Drug Deliv Formul. 2020;14(2):88–97. https://doi.org/10.1016/J.IJBIOMAC.2018.11.224.
• [22] Zhang S, Yu F, Chen J, Yan D, Gong D, Chen L, Chen J, Yao Q. A thin film comprising silk peptide and cellulose nanofibrils implanting on the electrospun poly(lactic acid) fibrous scaffolds for biomedical reconstruction. Int J Biol Macromol. 2023;251:126209. https://doi.org/10.1016/J.IJBIOMAC.2023.126209.
• [23] Prajapati VD, Chaudhari AM, Gandhi AK, Maheriya P. Pullulan based oral thin film formulation of zolmitriptan: Development and optimization using factorial design. Int J Biol Macromol. 2018;107:2075–2085. https://doi.org/10.1016/J.IJBIOMAC.2017.10.082.