EC Pharmacology And Toxicology

To improve patient compliance and experience, oral dissolving film (ODF) is a favorable drug delivery method. Advantages of using ODFs include bypassing the first pass effect, no degradation in the gastrointestinal tract, and quick onset of action. Films were prepared by using the casting method. Physical characterizations of the films were performed. Drug release studies and cytotoxic studies using dendritic cells were also conducted. An ex vivo permeability study was performed using the ionic liquid DABCO as a permeability enhancer and diphenhydramine hydrochloride as a model drug. In addition, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses were conducted. The results showed that ionic liquid DABCO-containing films disintegrate in < 5 minutes, have a neutral surface pH, and are noncytotoxic. Stability tests showed that there was no significant difference in appearance, physiochemical properties, and weight variation. Differential scanning calorimetry (DSC) analysis revealed films are in amorphous form. X-ray diffraction (XRD) analysis confirmed that the drug was not crystalline. Results suggest that films with the ionic liquid are capable of enhancing not only the permeability of the drug diphenhydramine hydrochloride but also the release of the drug from the film.

 Keywords: Ionic Liquid; 1,4-Diazabicyclo-Octane (DABCO); Oral Dissolving Film (ODF); Permeability Enhancer; Buccal Films; Permeability

1. M Malke., et al. “Formulation and evaluation of oxcarbazepine fast dissolve tablets”. Indian Journal of Pharmaceutical Sciences 2 (2007): 211-214.
2. N Souvik., et al. “Vildagliptin plasticized hydrogel film in the control of ocular inflammation after topical application: study of hydration and erosion behavior”. Zeitschrift für Physikalische Chemie 2 (2021): 275-290.
3. M Rajaram., et al. “Transcorneal permeation of diclofenac as a function of temperature from film formulation in presence of triethanolamine and benzalkonium chloride”. Colloids and Surfaces B: Biointerfaces1 (2014): 170-180.
4. S Groeger., et al. “Oral mucosal epithelial cells”. Frontiers in Immunology 10 (2019): 208.
5. Alipour Shohreh., et al. “Development and in vitro evaluation of fast-dissolving oral films of ondansetron hydrochloride”. Trends in Pharmaceutical Sciences1 (2015): 25-30.
6. Almeida Nilsa Maria Galvão., et al. “A novel dosage form for buccal administration of bupropion”. Brazilian Journal of Pharmaceutical Sciences1 (2015): 91-100.
7. Arun Arya., et al. “Fast dissolving oral films: an innovative drug delivery system and dosage form”. International Journal of ChemTech Research1 (2015): 576-583.
8. Chougule Pankaj C., et al. “Design and evaluation of formulated mouth dissolving film of domperidone and study the effect of concentration of polymers on drug release”. Asian Journal of Pharmaceutics4 (2017): 846-853.
9. European Directorate for the Quality of Medicines & HealthCare. 1 European Pharmacopoeia - 8^th Strasbourg: EDQM (2013).
10. Evans Kervin O. “Room-temperature ionic liquid cations act as short-chain surfactants and disintegrate a phospholipid bilayer”. Colloids and Surfaces A: Physicochemical and Engineering Aspects1-3 (2006): 11-17.
11. Gandhi Rajesh B and Joseph R Robinson. “Oral cavity as a site for bioadhesive drug delivery”. Advanced Drug Delivery Reviews 13 (1994): 43-74.
12. Hao Jinsong and Paul WS Heng. “Buccal delivery systems”. Drug Development and Industrial Pharmacy8 (2003): 821-832.
13. Hearnden Vanessa., et al. “New developments and opportunities in oral mucosal drug delivery for local and systemic disease”. Advanced Drug Delivery Reviews1 (2012): 16-28.
14. Hoffmann Eva Maria., et al. “Advances in orodispersible films for drug delivery”. Expert Opinion on Drug Delivery3 (2011): 299-316.
15. “ICH Requirements for Pharmaceutical”. Q1 Scientific (2017).
16. Kaza Rajesh., et al. “Formulation and characterization of gliclazide oral dissolving films”. Drug Delivery Letters 3 (2017): 185-192.
17. Kirkpatrick Douglas., et al. “UHPLC assay and impurity methods for diphenhydramine and phenylephrine hydrochloride oral solution”. Separation Science Plus1-2 (2020): 4-11.
18. Mahboob Muhammad Bilal Hassan., et al. “Oral films: a comprehensive review”. International Current Pharmaceutical Journal12 (2016): 111-117.
19. Monti Daniela., et al. “Ionic liquids as potential enhancers for transdermal drug delivery”. International Journal of Pharmaceutics1-2 (2017): 45-51.
20. Murthy AV., et al. “Formulation and evaluation of tramadol hydrochloride oral thin films”. International Journal of Pharmaceutical Sciences and Research 5 (2018): 1692-1698.
21. Pathare Yogyata S., et al. “Polymers used for fast disintegrating oral films: a review”. International Journal of Pharmaceutical Sciences Review and Research1 (2013): 169-178.
22. Schaffran Tanja., et al. “Toxicity of N,N,N-Trialkylammoniododecaborates as new anions of ionic liquids in cellular, liposomal and enzymatic test systems”. Green Chemistry9 (2009): 1458.
23. Teodorescu Mirela and Maria Bercea. “Poly(Vinylpyrrolidone) - A versatile polymer for biomedical and beyond medical applications”. Polymer - Plastics Technology and Engineering9 (2015): 923-943.
24. Uddin Mohammad Nasir., et al. “Overview and future potential of fast dissolving buccal films as drug delivery system for vaccines”. Journal of Pharmacy and Pharmaceutical Sciences: A Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques1 (2019): 388-406.
25. “Useful Numbers for Cell Culture”. Thermo Fisher Scientific (2021).