PARKİNSON TEDAVİSİ İÇİN RASAJİLİN MESİLAT MUKOADEZİF AĞIZDA DAĞILAN FİLM FORMÜLASYONLARI

Year 2023, Volume: 47 Issue: 1, 9 - 19, 20.01.2023

Meliha Güneş , Gökçe Turan , Armağan Dönmezer , Fadime Aydın Köse , Kevser Özgen Özer , Sinem Yaprak Karavana

https://doi.org/10.33483/jfpau.1150792

Abstract

Amaç: Bu makale, Parkinson Hastalığının oral olmayan tedavisi için Rasagilin mesilat (RM) ağızda dağılan filmlerin (ODF'ler) formülasyon çalışmalarını ve in vitro değerlendirmesini içermektedir. RM, özellikle yoğun hepatik biyotransformasyona uğrayan geri döndürülemez ve yüksek seçiciliğe sahip bir MAO-B inhibitörüdür. Karaciğerde metabolize edilir ve oral biyoyararlanımı yaklaşık %36 ve yarılanma ömrü 3 saattir. Bu özellikler, RM'nin bukkal ilaç dağıtımı için mükemmel bir aday olabileceğini göstermektedir.

Yöntem: RM'nin ODF'leri, solvent döküm yöntemiyle PEO kullanılarak hazırlandı. Bu formülasyonlar değerlendirilirken görünüş, ağırlık homojenliği, kalınlık, yüzey pH’sı, ilaç içeriği, şişme oranı, gerilme mukavemeti, mukoadezyon, in vitro ilaç salım çalışmaları ve stabilite gibi parametreler göz önünde bulundurulmuştur.

Sonuç ve Tartışma: Elde edilen sonuçlar, ODF'lerin RM uygulaması için etkili ve uygulanabilir bir yaklaşım olduğunu ve Parkinson tedavisi için mevcut oral dağıtım sistemlerine yeni bir alternatif olabileceğini göstermektedir.

Keywords

Ağızda dağılan film, bukkal uygulama, polietilen oksit, rasajilin mesilat

Supporting Institution

TÜBİTAK

Project Number

219S545

MUCOADHESIVE ORODISPERSIBLE FILM FORMULATIONS OF RASAGILINE MESYLATE FOR PARKINSON TREATMENT

Abstract

Objective: The article is included formulation studies and in vitro evaluation of orally dispersible Rasagiline mesylate (RM) orodispersible films (ODFs) for non-oral treatment of Parkinson's Disease. RM undergoes extensive hepatic biotransformation and is a highly selective and irreversible MAO-B inhibitor. It is metabolized in the liver and has an oral bioavailability of approximately 36% and a half-life of 3 hours. These properties suggest that RM may be an excellent candidate for buccal drug delivery.

Material and Method: ODFs of RM were prepared using PEO by the solvent casting method. While evaluating these formulations, parameters such as appearance, weight homogeneity, thickness, surface pH, drug content, swelling ratio, tensile strength, mucoadhesion, in vitro drug release studies and also stability were considered.

Result and Discussion: Obtained results show that ODFs are an effective and viable approach for RM delivery and may be a new alternative to existing oral delivery systems for Parkinson's treatment.

Keywords

Buccal delivery, orodispersible film, polyethylene oxide, rasagiline mesylate

Project Number

219S545

References

• 1. Pfeiffer RF.(2016). Non-motor symptoms in Parkinson’s disease. Park Relat Disord 22: S119–S122. [CrossRef]
• 2. Himanshu, Bhaskar R, Sharma N, Mehta M, Singh A, Yashwant, Yadav NS, Khatik GL, Verma S. (2017). Development and evaluation of buccoadhesive film of ropinirole hydrochloride for the treatment of Parkinson’s disease. Int J Drug Deliv Technol 7: 106–112. [CrossRef]
• 3. Rabey JM, Sagi I, Huberman M, Melamed E, Korczyn A, Giladi N, Inzelberg R, Djaldetti R, Klein C, Berecz G.( 2000). Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson’s disease: A double-blind study as adjunctive therapy to levodopa. Clin Neuropharmacol 23: 324–330 [CrossRef]
• 4. Bukka R, Prakasam K, Patel CD. (2010). Preparation and Evaluation of Intraoral Drug Delivery System for Rasagiline mesylate. Int J Pharm Sci Drug Res 2: 294–301. [CrossRef]
• 5. Hoffmann EM, Breitenbach A, Breitkreutz J.( 2011). Advances in orodispersible films for drug delivery. Expert Opin Drug Deliv 8: 299–316. [CrossRef]
• 6. Irfan M, Rabel S, Bukhtar Q, Qadir MI, Jabeen F, Khan A. (2016). Orally disintegrating films: A modern expansion in drug delivery system. Saudi Pharm J 24: 537–546. [CrossRef]
• 7. Ravi PR, Aditya N, Cherian L, Patil S.(2013). LC Method for Determination of Rasagiline Mesylate in Different Plasma Matrices and its Application to Oral Pharmacokinetic Study in Rabbits. J Chromatogr Sci. 51(1):1-7. [CrossRef]
• 8. 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 “Formulation and Evaluation of Fast Dissolving Oral Film of Dicyclomine as potential route of Buccal Delivery” Int. J. Drug Dev. & Res, 4(2), 408–417. Retrieved from http://www.ijddr.in
• 9. Hosny KM, El-Say KM, Ahmed OA. (2016). Optimized sildenafil citrate fast orodissolvable film: A promising formula for overcoming the barriers hindering erectile dysfunction treatment. Drug Deliv 23: 355–361. [CrossRef]
• 10. Bahri-Najafi, R., Tavakoli, N., Senemar, M., & Peikanpour, M. (2014). Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive Buccal film. Research in Pharmaceutical Sciences, 9(3), 213–223. Retrieved from /pmc/articles/PMC4311287/
• 11. Mashru RC, Sutariya VB, Sankalia MG, Parikh PP. (2005). Development and evaluation of fast-dissolving film of salbutamol suplhate. Drug Dev Ind Pharm 31: 25–34. [CrossRef]
• 12. Çoban G, Aydın Köse F. (2019). Synthesis, biological evaluations and molecular modelling studies of novel indolin-2-ones designing as FGFR inhibitors. Saudi Pharm J. 27(7):952-967. [CrossRef]
• 13. Cheaburu-Yilmaz CN, Yilmaz O, Kose FA, Bibire N. (2019). Chitosan-graft-poly(N-isopropylacrylamide)/PVA cryogels as carriers for mucosal delivery of voriconazole. Polymers (Basel) 11: 1432. [CrossRef]
• 14. Nair AB, Shah J, Jacob S, Al-Dhubiab BE, Patel V, Sreeharsha N, Shinu P.( 2021). Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation. Pharmaceutics 13: 728. [CrossRef]
• 15. Nair AB, Al-Dhubiab BE, Shah J, Jacob S, Saraiya V, Attimarad M, SreeHarsha N, Akrawi SH, Shehata TM.( 2020). Mucoadhesive buccal film of almotriptan improved therapeutic delivery in rabbit model. Saudi Pharm J 28: 201–209. [CrossRef]
• 16. Szabó P, Daróczi TB, Tóth G, Zelkó R. (2016). In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets. J Pharm Biomed Anal 131: 156–159. [CrossRef]
• 17. Jovanović M, Tomić N, Cvijić S, Stojanović D, Ibrić S, Uskoković P.( 2021). Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. Pharmaceutics 13: 1–19. [CrossRef]
• 18. Singh, T. P., Singh, R. K., Shah, J. N., & Mehta, T. A. (2014). Mucoadhesive bilayer buccal patches of verapamil hydrochloride: Formulation development and characterization. International Journal of Pharmacy and Pharmaceutical Sciences, 6(4), 234–241. Retrieved from https://innovareacademics.in/journal/ijpps/Vol6Issue4/8975.pdf
• 19. Rençber S, Karavana SY, Yilmaz FF, Eraç B, Nenni M, Gurer-Orhan H, Limoncu MH, Güneri P, Ertan G.(2019). Formulation and evaluation of fluconazole loaded oral strips for local treatment of oral candidiasis. [CrossRef]
• 20. Arslan Azizoglu G, Tuncay Tanriverdi S, Aydin Kose F, Ballar Kirmizibayrak P, Ozer O. (2017). Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions. AAPS PharmSciTech 18: 2987–2998. [CrossRef]