ZEYTİN YAPRAĞI POLİFENOLLERİ YÜKLÜ MUKOADHESİF ORAL FİLMLER

Abstract

İlaç aktarım sistemleri arasında, ağızda çözünen filmler (AÇF'ler) birçok avantajı olan bir ilaç uygulama şeklidir. Yutma gerektiren geleneksel ilaç verme yöntemleri ile özellikle pediatrik ve geriatrik hastalarda bazı sorunlar yaşanabilir. Bu gibi durumlarda, ilacın ağızda dağılmış bir filmle verilmesi büyük kolaylık sağlar. Bu çalışmada, filmlerin hazırlanması için solvent döküm yöntemi tercih edilmiştir. Biyopolimer oranı ve yüklenmiş zeytin yaprağı ekstraktının film özellikleri üzerindeki etkisi, merkezi kompozit deneysel tasarım ile araştırılmıştır. Hazırlanan filmlerin karakterizasyon çalışmaları AFM, SEM ve FTIR analizleri ile yapılmıştır. Karakterizasyon çalışmalarına dayanarak, en iyi dört formülasyon seçilmiş ve araştırmada bu formülasyonlara odaklanılmıştır. Formülasyon 8, esneklik ve homojenlik gibi daha iyi film özellikleri, daha düşük parçalanma süresi (200 s) ve daha yüksek antioksidan kapasitesi (3.21 mM TEAC/g AÇF) nedeniyle 17 formülasyon arasından optimum formülasyon olarak seçilmiştir. Elde edilen veriler, hazırlanan ağızda çözünen filmlerle zeytin yaprağı polifenollerinin aktarımının mümkün olduğunu ortaya koymuştur.

Keywords

• Ağızda Çözünen Film
• Oral Film
• Karboksimetil Kitosan
• Bamya Zamkı
• Zeytin Yaprağı Ekstraktı

OLIVE LEAF POLYPHENOLS LOADED MUCOADHESIVE ORAL FILMS

Abstract

Among drug delivery systems, mouth dissolving films (MDFs) are a form of drug administration with many advantages. Some problems could be experienced, primarily in pediatric and geriatric patients with conventional drug delivery methods as swallowing. It is of great convenience to dispensing the drug with a film dispersed in the mouth in such cases. In this study, for the preparation of films, the solvent casting method was preferred. The effect of biopolymer ratio and loaded olive leaf extract on the film properties were investigated with the central composite experimental design. Characterization studies of the prepared films were done with AFM, SEM, and FTIR analysis. Based on the characterization studies, the four best formulations were chosen, and further investigations were focused on these formulations. Formulation 8 was chosen as the optimum formulation among 17 formulations due to its better film properties as flexibility and homogeneity, lower disintegration time 200s, and a higher antioxidant capacity 3.21 mM TEAC/g MDF. The obtained data revealed that it is possible to deliver olive leaf polyphenols with the prepared mouth dissolving films.

Keywords

• Mouth Dissolving Film
• Oral Film
• Carboxymethyl Chitosan
• Okra Gum
• Olive Leaf Extract

References

1. Al-Rimawi, F. (2014). Development and validation of a simple reversed-phase HPLC-UV method for determination of oleuropein in olive leaves. Journal of Food and Drug Analysis, 22(3), 285–289.
2. Altıok, E., Bayçın, D., Bayraktar, O., & Ülkü, S. (2008). Isolation of polyphenols from the extracts of olive leaves (Olea europaea L.) by adsorption on silk fibroin. Separation and Purification Technology, 62(2), 342–348.
3. Arya, A., Chandra, A., Sharma, V., & Pathak, K. (2010). Fast Dissolving Oral Films: An Innovative Drug Delivery System and Dosage Form. International Journal of ChemTech Research, 2(1), 576–583.
4. Ashok Pawar, H., & Kamat, S. R. (2017). Development and Evaluation of Mouth Dissolving Film of Ondansetron Hydrochloride Using Hpmc E 5 in Combination with Taro Gum and Other Commercially Available Gums. Journal of Molecular Pharmaceutics & Organic Process Research, 05(01), 1–9.
5. Basal, G., Tetik, G. D., Kurkcu, G., Bayraktar, O., Gurhan, I. D., & Atabey, A. (2016). Olive leaf extract loaded silk fibroin/hyaluronic acid nanofiber webs for wound dressing applications. Digest Journal of Nanomaterials and Biostructures, 11(4), 1113–1123.
6. Bharti, K., Mittal, P., & Mishra, B. (2019). Formulation and characterization of fast dissolving oral films containing buspirone hydrochloride nanoparticles using design of experiment. Journal of Drug Delivery Science and Technology, 49, 420–432.
7. Cejudo Bastante, C., Casas Cardoso, L., Fernández Ponce, M. T., Mantell Serrano, C., & Martínez de la Ossa-Fernández, E. J. (2018). Characterization of olive leaf extract polyphenols loaded by supercritical solvent impregnation into PET/PP food packaging films. Journal of Supercritical Fluids, 140, 196–206.
8. Chandra Mohan, C., Harini, K., Vajiha Aafrin, B., Lalitha priya, U., Maria jenita, P., Babuskin, S., et al. (2018). Extraction and characterization of polysaccharides from tamarind seeds, rice mill residue, okra waste and sugarcane bagasse for its Bio-thermoplastic properties. Carbohydrate Polymers, 186, 394–401.

9. Dahiya, M., Saha, S., & Shahiwala, A. (2009). A Review on Mouth Dissolving Films. Current Drug Delivery, 6(5), 469–476.
10. El, S. N., & Karakaya, S. (2009). Olive tree (Olea europaea) leaves: Potential beneficial effects on human health. Nutrition Reviews, 67(11), 632-638.
11. Erdoğan, İ., Bayraktar, O., Uslu, M. E., & Tüncel, Ö. (2018). Wound Healing Effects of Various Fractions of Olive Leaf Extract ( OLE ) on Mouse Fibroblasts. Romanian Biotechnological Letters, 23(6), 14217–14228.
12. Erdogan, I., Demir, M., & Bayraktar, O. (2015). Olive leaf extract as a crosslinking agent for the preparation of electrospun zein fibers. Journal of Applied Polymer Science, 132(4).
13. Garcia, V. A. dos S., Borges, J. G., Vanin, F. M., & Carvalho, R. A. de. (2020). Orally disintegrating films of biopolymers for drug delivery. In Biopolymer Membranes and Films (pp. 289–307).
14. Gittings, S., Turnbull, N., Henry, B., Roberts, C. J., & Gershkovich, P. (2015). Characterisation of human saliva as a platform for oral dissolution medium development. European Journal of Pharmaceutics and Biopharmaceutics, 91, 16–24.
15. Iqbal, D. N., Tariq, M., Khan, S. M., Gull, N., Sagar Iqbal, S., Aziz, A., et al. (2020). Synthesis and characterization of chitosan and guar gum based ternary blends with polyvinyl alcohol. International Journal of Biological Macromolecules, 143, 546–554.
16. Irfan, M., Rabel, S., Bukhtar, Q., Qadir, M. I., Jabeen, F., & Khan, A. (2016). Orally disintegrating films: A modern expansion in drug delivery system. Saudi Pharmaceutical Journal. Elsevier B.V.
17. Jiang, S., Zou, L., Hou, Y., Qian, F., Tuo, Y., Wu, X., et al. (2020). The influence of the addition of transglutaminase at different phase on the film and film forming characteristics of whey protein concentrate-carboxymethyl chitosan composite films. Food Packaging and Shelf Life, 25, 100546.
18. Kalu, V. D., Odeniyi, M. A., & Jaiyeoba, K. T. (2007). Matrix properties of a new plant gum in controlled drug delivery. Archives of Pharmacal Research, 30(7), 884–889.
19. Karki, S., Kim, H., Na, S. J., Shin, D., Jo, K., & Lee, J. (2016). Thin films as an emerging platform for drug delivery. Asian Journal of Pharmaceutical Sciences. Shenyang Pharmaceutical University, 11(5),559-574.
20. Moudache, M., Colon, M., Nerín, C., & Zaidi, F. (2016). Phenolic content and antioxidant activity of olive by-products and antioxidant film containing olive leaf extract. Food Chemistry, 212, 521–527.
21. Nagpal, M., Aggarwal, G., Jain, U. K., & Madan, J. (2017). Okra fruit gum-chitosan impregnated polymer network films: Formulation and substantial depiction. Asian Journal of Pharmaceutical and Clinical Research, 10(10), 219–222.
22. Nair, A. B., Al-Dhubiab, B. E., Shah, J., Vimal, P., Attimarad, M., & Harsha, S. (2018). Development and evaluation of palonosetron loaded mucoadhesive buccal films. Journal of Drug Delivery Science and Technology, 47, 351–358.
23. Navarro, M., & Morales, F. J. (2017). Evaluation of an olive leaf extract as a natural source of antiglycative compounds. Food Research International, 92, 56–63.
24. Nayak, A. K., Ahmad, S. A., Beg, S., Ara, T. J., & Hasnain, M. S. (2018). Drug delivery: Present, past, and future of medicine. In Applications of Nanocomposite Materials in Drug Delivery (pp. 255–282). Elsevier.
25. Nayak, A. K., Ara, T. J., Saquib Hasnain, M., & Hoda, N. (2018). Okra gum-alginate composites for controlled releasing drug delivery. In Applications of Nanocomposite Materials in Drug Delivery (pp. 761–785). Elsevier.
26. Ogaji, I., & Nnoli, O. (2014). Film coating potential of okra gum using paracetamol tablets as a model drug. Asian Journal of Pharmaceutics, 4(2), 130-134.
27. Patel, V. F., Liu, F., & Brown, M. B. (2011). Advances in oral transmucosal drug delivery. Journal of Controlled Release. J Control Release. 153(2), 106-116.
28. Pinhas, M. D., Peled, H. V., 2010, Mucoadhesion: a review of characterization techniques. Expert Opinion Drug Delivery, 7(2), 259-271.
29. Rahmanian, N., Jafari, S. M., & Wani, T. A. (2015). Bioactive profile, dehydration, extraction and application of the bioactive components of olive leaves. Trends in Food Science and Technology.42(2), 150-172.
30. Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine, 26(9–10), 1231–1237.
31. Ruiz, H. A., Cerqueira, M. A., Silva, H. D., Rodríguez-Jasso, R. M., Vicente, A. A., & Teixeira, J. A. (2013). Biorefinery valorization of autohydrolysis wheat straw hemicellulose to be applied in a polymer-blend film. Carbohydrate Polymers, 92(2), 2154–2162.
32. Shariatinia, Z. (2018). Carboxymethyl chitosan: Properties and biomedical applications. International Journal of Biological Macromolecules, 120, 1406–1419.
33. Speer, I., Steiner, D., Thabet, Y., Breitkreutz, J., & Kwade, A. (2018). Comparative study on disintegration methods for oral film preparations. European Journal of Pharmaceutics and Biopharmaceutics, 132, 50–61.
34. Suriyatem, R., Auras, R. A., & Rachtanapun, P. (2018). Improvement of mechanical properties and thermal stability of biodegradable rice starch–based films blended with carboxymethyl chitosan. Industrial Crops and Products, 122, 37–48.
35. Tomar, A., Sharma, K., Chauhan, N. S., Mittal, A., & Bajaj, U. (2012). Formulation and Evaluation of Fast Dissolving Oral Film of Dicyclomine as potential route of Buccal Delivery. International Journal of Drug Development and Research (Vol. 4). iMedPub.
36. Verma, U., Rajput, R., & Naik, J. B. (2018). Development and characterization of Fast Dissolving Film of Chitosan embedded Famotidine Using 32 Full Factorial Design Approach. In Materials Today: Proceedings, 5, 408–414.
37. Vilar, G., Tulla-Puche, J., & Albericio, F. (2012). Polymers and Drug Delivery Systems. Current Drug Delivery, 9(4), 367–394.
38. Wang, L.-C., Chen, X.-G., Yu, L.-J., & Li, P.-W. (2007). Controlled drug release through carboxymethyl-chitosan/poly(vinyl alcohol) blend films. Polymer Engineering & Science, 47(9), 1373–1379.
39. Zaharuddin, N. D., Noordin, M. I., & Kadivar, A. (2014). The use of hibiscus esculentus (Okra) gum in sustaining the release of propranolol hydrochloride in a solid oral dosage form. BioMed Research International, 2014, 1-8.