Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization
Elif Nur Tunç, Afife Büşra Uğur Kaplan, Yaşar Furkan Kilinboz, Meltem ÇetinBackground and Aims: Epilepsy is one of the most disabling and most common neurological disorders, affecting approximately 65 million people of all age groups worldwide. When there is no response to monotherapy in the treatment of epilepsy, the combined use of Carbamazepine (CARBA) and Levetiracetam (LEV), which have different mechanisms of action, can be additive/synergistic and may be useful in the clinic. The aim of our study is to develop a fixed-dose combination (FDC)- nanoemulsion (NE) formulation containing CARBA and LEV for the treatment of epilepsy.
Methods: Blank NE (BLNK-NE) and CARBA+LEV-FDC-NE formulations were prepared and carried out the in vitro characterization studies [morphological analysis, centrifugation test, droplet size (DS), polydispersity index (PDI), zeta potential (ZP), viscosity and pH measurements, FT-IR analysis, the percent entrapment efficiency (EE%), and in vitro release study].
Results: The DS, PDI, pH, and ZP values for the BLNK-NE formulation were found to be 117.63±3.82 nm, 0.240±0.014, 4.62±0.03, and (-)26.07±3.04 mV, respectively. For the CARBA+LEV-FDC-NE formulation, the DS, PDI, pH, and ZP values were determined as 137.56±3.11 nm, 0.225±0.013, 4.60±0.06, and (-)21.62±0.29 mV, respectively. The EE% values obtained for CARBA+LEV-FDC-NE were 97.33±0.56% (for CARBA) and 96.73±0.91% (for LEV).
Conclusion: The CARBA+LEV-FDC-NE formulation was successfully prepared. This formulation had suitable in vitro characterization results.
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Referanslar
- Alkhatib, M.H., Bawadud, R.S., & Gashlan, H.M. (2020). Incorpora-tion of docetaxel and thymoquinone in borage nanoemulsion potentiates their antineoplastic activity in breast cancer cells. Scientific Reports, 10(1), 18124. doi:10.1038/s41598-020-75017-5 google scholar
- Alkreathy, H., Alkhatib, M., Al-thepyani, M., Balamash, K., Alghamdi, S., Karim, S., & Ahmad, A. (2020). Synergistic antitumor activity of doxorubicin and atorvastatin combination loaded nanoemulsion in mice. International Journal of Pharmacology, 16(4), 330-342. doi:10.3923/ijp.2020.330.342 google scholar
- Beydoun, A., DuPont, S., Zhou, D., Matta, M., Nagire, V., & Lagae, L. (2020). Current role of carbamazepine and oxcarbazepine in the management of epilepsy. Seizure, 83, 251-263. doi:10.1016/j. seizure.2020.10.018 google scholar
- Devinsky, O., Vezzani, A., O’Brien, T.J., Jette, N., Scheffer, I.E., de Cur-tis, M., & Perucca, P. (2018). Epilepsy. Nature Reviews Disease Prim-ers, 4(1), 1-24. doi:10.1038/nrdp.2018.24 google scholar
- Djekic, L., Markovic, B., Micov, A., Tomic, M., Pecikoza, U., & Stepanovic-Petrovic, R. (2021). Percutaneous delivery of leve-tiracetam as an alternative to topical nonsteroidal anti-inflam-matory drugs: formulation development, in vitro and in vivo characterization. Drug Delivery and Translational Research, 11(1), 227-241. doi:10.1007/s13346-020-00787-4 google scholar
- Echeverri, J.D., Alhajj, M.J., Montero, N., Yarce, C.J., Barrera-Ocampo, A., & Salamanca, C. H. (2020). Study of In Vitro and In Vivo Carbam-azepine Release from Coarse and Nanometric Pharmaceutical Emul-sions Obtained via Ultra-High-Pressure Homogenization. Pharma-ceuticals (Basel, Switzerland), 13(4), E53. doi:10.3390/ph13040053 google scholar
- Ensom, M.H.H., Decarie, D., & Rudolph, S. (2011). Stability of le-vetiracetam in extemporaneously compounded suspensions. The Canadian Journal of Hospital Pharmacy, 64(3), 207-211. doi:10.4212/cjhp.v64i3.1024. google scholar
- Green, S.F., Nguyen, P., Kaalund-Hansen, K., Rajakulendran, S., & Murphy, E. (2020). Effectiveness, retention, and safety of modified ketogenic diet in adults with epilepsy at a tertiary-care centre in the UK. Journal of Neurology, 267(4), 1171-1178. doi:10.1007/ s00415-019-09658-6 google scholar
- Gupta, A. (2020). Chapter 21 - Nanoemulsions. In E. J. Chung, L. Leon, & C. Rinaldi (Eds.), Nanoparticles for Biomedical Applications (pp. 371-384). Elsevier. doi:10.1016/B978-0-12-816662-8.00021-7 google scholar
- Hu, M., Xie, F., Zhang, S., Qi, B., & Li, Y. (2021). Effect of nanoemul-sion particle size on the bioavailability and bioactivity of perilla oil in rats. Journal of Food Science, 86(1), 206-214. doi:10.1111/1750-3841.15537 google scholar
- Kandilli, B., Uğur, A.B., Çetin, M., & Miloğlu, F.D. (2018). A simple HPLC-UV method for simultaneous determination of levetirace-tam and carbamazepine, Hacettepe University Journal of the Fac-ulty of Pharmacy, 38(2), 58-64. google scholar
- Kandilli, B., Ugur Kaplan, A.B., Cetin, M., Taspinar, N., Ertugrul, M.S., Aydin, I.C., & Hacimuftuoglu, A. (2020). Carbamazepine and leveti-racetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies. Drug Development and Industrial Pharmacy, 46(7), 1063-1072. doi:10.1080/03639045.2020.1769127 google scholar
- Kanner, A.M., & Bicchi, M. M. (2022). Antiseizure medications for adults with epilepsy: A Review. JAMA, 327(13), 1269-1281. doi:10.1001/jama.2022.3880 google scholar
- Kelmann, R.G., Kuminek, G., Teixeira, H.F., & Koester, L.S. (2007). Carbamazepine parenteral nanoemulsions prepared by sponta-neous emulsification process. International Journal of Pharmaceu-tics, 342(1-2), 231-239. doi:10.1016/j.ijpharm.2007.05.004 google scholar
- Kim, D.W., & Weon, K.Y. (2021). Pharmaceutical application and de-velopment of fixed-dose combination: dosage form review. Jour-nal of Pharmaceutical Investigation, 51(5), 555-570. doi:10.1007/ s40005-021-00543-x google scholar
- Kumar, A., Maini, K., & Kadian, R. (2022). Levetiracetam. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Retrived from https://www.ncbi.nlm.nih.gov/books/NBK499890/ google scholar
- Lovelyn, C., & Attama, A.A. (2011). Current state of nanoemulsions in drug delivery. Journal of Biomaterials and Nanobiotechnology, 02(05), 626. doi:10.4236/jbnb.2011.225075 google scholar
- Lyseng-Williamson, K.A. (2011). Levetiracetam: a review of its use in epilepsy. Drugs, 71(4), 489-514. doi:10.2165/11204490-000000000-00000 google scholar
- Maan, J. S., Duong, T. vi H., & Saadabadi, A. (2022). Carbamazepine. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Retrived from https://www.ncbi.nlm.nih.gov/books/NBK482455/ google scholar
- Mahajan, H.S., & Patil, N.D. (2021). Nanoemulsion containing a synergistic combination of curcumin and quercetin for nose-to-brain delivery: In vitro and in vivo studies. Asian Pacific Journal of Tropical Biomedicine, 11(11), 510. doi:10.4103/2221-1691.328058 google scholar
- Mahamat Nor, S.B., Woi, P.M., & Ng, S.H. (2017). Characterisation of ionic liquids nanoemulsion loaded with piroxicam for drug deliv-ery system. Journal of Molecular Liquids, 234, 30-39. doi:10.1016/j. molliq.2017.03.042 google scholar
- Makinen, J., Rainesalo, S., Raitanen, J., & Peltola, J. (2017). The effect of newer antiepileptic drugs in combination therapy. Epilepsy Re-search, 132, 15-20. doi:10.1016/j.eplepsyres.2017.02.020 google scholar
- Nastiti, C.M.R R., Ponto, T., Abd, E., Grice, J.E., Benson, H.A.E., & Rob-erts, M.S. (2017). Topical nano and microemulsions for skin deliv-ery. Pharmaceutics, 9(4), E37. doi:10.3390/pharmaceutics9040037 google scholar
- Pangeni, R., Choi, S.W., Jeon, O.C., Byun, Y., & Park, J.W. (2016). Multiple nanoemulsion system for an oral combinational de-livery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation. International Journal of Nanomedicine, 11, 6379-6399. doi:10.2147/IJN.S121114 google scholar
- Park, K.M., Kim, S.E., & Lee, B.I. (2019). Antiepileptic drug therapy in patients with drug-resistant epilepsy. Journal of Epilepsy Research, 9(1), 14-26. doi:10.14581/jer.19002 google scholar
- Patel, R.J., & Parikh, R.H. (2020). Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies. International Journal of Pharmaceutics, 585, 119486. doi:10.1016/j.ijpharm.2020.119486 google scholar
- Petrusevska, M., Berglez, S., Krisch, I., Legen, I., Megusar, K., Peter-nel, L.,... Dressman, J. (2015). Biowaiver monographs for immedi-ate release solid oral dosage forms: levetiracetam. Journal of Phar-maceutical Sciences, 104(9), 2676-2687. doi:10.1002/jps.24350 google scholar
- Prokhorov, D.I., Sariev, A. K., Abramov, D.A., Voronina, T.A., Kapitsa, I.G., Zhuravko, A.S., . Seifulla, R.D. (2014). Experimental investiga-tion of pharmacodynamics and pharmacokinetics of carbamaze-pine nanoemulsion. Bulletin of Experimental Biology and Medicine, 157(6), 742-746. doi:10.1007/s10517-014-2657-z google scholar
- Rahman, M., Islam, F., Rahman, A., Ahmed, T., Uddin, M.B., Sha-heen, S.M., & Khushi, S.Y. (2020). Present and future prospect of combination drugs therapy. World Journal of Pharmaceutical Re-search, 9(3), 1625-1638. google scholar
- Rajadhyaksha, N.S., Jain, S.P., & Amin, P.D. (2007). Carbamazepine: Stability indicating HPLC assay method. Analytical Letters, 40(13), 2506-2514. doi:10.1080/00032710701583557 google scholar
- Rehman, A.U., Akram, S., Seralin, A., Vandamme, T., & Anton, N. (2020). Chapter 21 - Lipid nanocarriers: Formulation, properties, and applications. In P. Nguyen-Tri, T.-O. Do, & T. A. Nguyen (Eds.), Smart Nanocontainers (pp. 355-382). Elsevier. doi:10.1016/B978-0-12-816770-0.00021-6 google scholar
- Rosso, A., Lollo, G., Chevalier, Y., Troung, N., Bordes, C., Bourgeois, S., . Briançon, S. (2020). Development and structural character-ization of a novel nanoemulsion for oral drug delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 593, 124614. doi:10.1016/j.colsurfa.2020.124614 google scholar
- Sabjan, K.B., Munawar, S.M., Rajendiran, D., Vinoji, S.K., & Kasina-than, K. (2020). Nanoemulsion as oral drug delivery - a review. Current Drug Research Reviews, 12(1), 4-15. google scholar
- Santos, J.,Trujillo-Cayado, L.A., Carrillo, F., Lopez-Castejon, M. L., & Alfaro-Rodrfguez, M. C. (2022). Relation between droplet size dis-tributions and physical stability for zein microfluidized emulsions. Polymers, 14(11), 2195. doi:10.3390/polym14112195 google scholar
- Sarhan, E.M., Walker, M.C., & Selai, C. (2016). Evidence for efficacy of combination of antiepileptic drugs in treatment of epilepsy. Jour-nal of Neurology Research, 5(6), 267-276. doi:10.14740/jnr.v5i6.356 google scholar
- Sigward, E., Mignet, N., Rat, P., Dutot, M., Muhamed, S., Guigner, J.-M., . Crauste-Manciet, S. (2013). Formulation and cytotoxic-ity evaluation of new self-emulsifying multiple W/O/W nano-emulsions. International Journal of Nanomedicine, 8, 611-625. doi:10.2147/IJN.S35661 google scholar
- Ugur Kaplan, A.B., Cetin, M., Orgul, D., Taghizadehghalehjoughi, A., Hacımuftuoglu, A., & Hekimoglu, S. (2019). Formulation and in vitro evaluation of topical nanoemulsion and nanoemulsion-based gels containing daidzein. Journal of Drug Delivery Science and Technology, 52, 189-203. doi:10.1016/j.jddst.2019.04.027 google scholar
- Uzunovic, A., Vranic, E., & Hadzidedic, S. (2010). Impairment of the in vitro release of carbamazepine from tablets. Bosnian Journal of Basic Medical Sciences, 10(3), 234-238. google scholar
- Vazquez-Blanco, S., Gonzalez-Freire, L., Davila-Pousa, M. C., & Cre-spo-Diz, C. (2018). pH determination as a quality standard for the elaboration of oral liquid compounding formula. Farmacia Hospi-talaria: Organo Oficial De Expresion Cientifica De La Sociedad Espa-nola De Farmacia Hospitalaria, 42(6), 221-227. doi:10.7399/fh.10932 google scholar
- Wik, J., Bansal, K.K., Assmuth, T., Rosling, A, Rosenholm, J.M. (2020). Facile methodology of nanoemulsion preparation using oily poly-mer for the delivery of poorly soluble drugs. Drug Delivery and Trans-lational Research, 10, 1228-1240. doi: 10.1007/s13346-019-00703-5 google scholar
- Wirrell, E., Tinuper, P., Perucca, E., & Moshe, S.L. (2022). Introduc-tion to the epilepsy syndrome papers. Epilepsia, 63(6), 1330-1332. doi:10.1111/epi.17262 google scholar
- Yi, Z.-M., Wen, C., Cai, T., Xu, L., Zhong, X.-L., . Zhai, S.-D. (2018). Levetiracetam for epilepsy: an evidence map of efficacy, safety and economic profiles. Neuropsychiatric Disease and Treatment, 15, 1-19. doi:10.2147/NDT.S181886 google scholar
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DIŞA AKTAR
APA
Tunç, E.N., Uğur Kaplan, A.B., Kilinboz, Y.F., & Çetin, M. (2023). Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization. İstanbul Journal of Pharmacy, 53(2), 133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106
AMA
Tunç E N, Uğur Kaplan A B, Kilinboz Y F, Çetin M. Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization. İstanbul Journal of Pharmacy. 2023;53(2):133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106
ABNT
Tunç, E.N.; Uğur Kaplan, A.B.; Kilinboz, Y.F.; Çetin, M. Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization. İstanbul Journal of Pharmacy, [Publisher Location], v. 53, n. 2, p. 133-139, 2023.
Chicago: Author-Date Style
Tunç, Elif Nur, and Afife Büşra Uğur Kaplan and Yaşar Furkan Kilinboz and Meltem Çetin. 2023. “Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization.” İstanbul Journal of Pharmacy 53, no. 2: 133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106
Chicago: Humanities Style
Tunç, Elif Nur, and Afife Büşra Uğur Kaplan and Yaşar Furkan Kilinboz and Meltem Çetin. “Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization.” İstanbul Journal of Pharmacy 53, no. 2 (Dec. 2024): 133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106
Harvard: Australian Style
Tunç, EN & Uğur Kaplan, AB & Kilinboz, YF & Çetin, M 2023, 'Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization', İstanbul Journal of Pharmacy, vol. 53, no. 2, pp. 133-139, viewed 14 Dec. 2024, https://doi.org/10.26650/IstanbulJPharm.2023.1201106
Harvard: Author-Date Style
Tunç, E.N. and Uğur Kaplan, A.B. and Kilinboz, Y.F. and Çetin, M. (2023) ‘Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization’, İstanbul Journal of Pharmacy, 53(2), pp. 133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106 (14 Dec. 2024).
MLA
Tunç, Elif Nur, and Afife Büşra Uğur Kaplan and Yaşar Furkan Kilinboz and Meltem Çetin. “Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization.” İstanbul Journal of Pharmacy, vol. 53, no. 2, 2023, pp. 133-139. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2023.1201106
Vancouver
Tunç EN, Uğur Kaplan AB, Kilinboz YF, Çetin M. Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization. İstanbul Journal of Pharmacy [Internet]. 14 Dec. 2024 [cited 14 Dec. 2024];53(2):133-139. Available from: https://doi.org/10.26650/IstanbulJPharm.2023.1201106 doi: 10.26650/IstanbulJPharm.2023.1201106
ISNAD
Tunç, ElifNur - Uğur Kaplan, AfifeBüşra - Kilinboz, YaşarFurkan - Çetin, Meltem. “Nanoemulsion formulation containing carbamazepine and levetiracetam: Development and in vitro characterization”. İstanbul Journal of Pharmacy 53/2 (Dec. 2024): 133-139. https://doi.org/10.26650/IstanbulJPharm.2023.1201106