Dilaltından İlaçların Taşınması ve Laboratuvar Hayvanlarındaki Uygulamaları

Öz

Dilaltı yoldan sistemik ilaç taşınması, farmakolojik etkinin hemen başlamasını sağlama arzusundan doğmuştur. Disfaji (yutma güçlüğü), tüm yaş gruplarında oral katı dozaj formlarını yutmakta güçlük çeken hastaların ortak sorunudur. Özellikle yaşlılarda, çocuklarda, zihinsel engellilerde, mide bulantısı olan veya sıvı alımı/diyeti azaltılmış kişilerde yutma problemlidir. İlacın dilaltı yoldan emilimi, oral yoldan 3 ila 10 kat daha fazladır. Dilaltı absorpsiyon çoğunlukla hızlıdır, fakat aynı zamanda süresi dekısadır. Karaciğerden ilk geçiş etkisi ve ayrıca gastrik bozulma da önlenir, böylece biyoyararlanım artar. Bu derlemenin amacı, dilaltı ilaç taşıma sistemlerinin ve bunlarla ilişkili ürünlerin geliştirilmesine rehberlik sağlamak için dilaltı uygulama bölgesinin fizyolojisini incelemek ve ilaçlar açısından değerlendirmek, literatürde yapılan hayvan modelli çalışmalar ile dilaltı uygulama yolunun önemini analiz etmektir.

Anahtar Kelimeler

• Biyoyararlanım
• dilaltı
• disfaji
• hayvan modeli
• ilk geçiş etkisi

Sublingual Drug Delivery and Applications in Laboratory Animals

Öz

Systemic drug delivery via sublingual route arose from the desire to ensure the immediate onset of pharmacological action. Dysphagia (difficulty swallowing) is a commonproblem for patients of all age groups who have difficulty swallowing oral solid dosage forms. It is especially a problem in the elderly, children, mentally handicapped people, people with nauseaor reduced fluid intake/diet. Sublingual absorption of the drug is 3 to 10 times greater than orally. Sublingual absorption is usually rapid, but also short in duration. The first-pass effect through the liver as well as gastric degradation is prevented, thus increasing the bioavailability. The aim of this review is to examine the physiology of the sublingual administration site and to evaluate it in terms of drugs, to provide guidance for the development of the sublingual drug delivery systems and their related products, and to analyze the importance of the sublingual administration route with animal model studies in the literature.

Anahtar Kelimeler

• Animal model
• Bioavailability
• dysphagia
• first-pass effect
• sublingual.

Kaynakça

1. Bae, J., Johnston, TA., Chaiittianan, R., Sutthanut, K., Jay, M., Marson, L., 2018. Characterization and in vivo efficacy of a heptapeptide ODT formulation for the treatment of neurogenic bladder dysfunction. Int J Pharm, 536(1), 397-404.
2. Bayrak, Z., Tas, C., Tasdemir, U., Erol, H., Ozkan, C. K., Savaser,A., Ozkan, Y., 2011. Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: In vitro and in vivo evaluation. Eur J Pharm Biopharm, 78(3), 499-505.
3. Bhati, R., Nagrajan, RK., 2012. A detailed review on oral mucosal drug delivery system. Int J Pharm Sci Res, 3(3), 659.
4. Brandl, M., Bauer-Brandl, A., 2019. Oromucosal drug delivery: Trends in in-vitro biopharmaceutical assessment of new chemical entities and formulations. Eur J Pharm Sci, 128, 112-117.
5. Dali, MM., Moench, PA., Mathias, NR., Stetsko, PI., Heran, CL., Smith, RL., 2006. A rabbit model for sublingual drug delivery: comparison with human pharmacokinetic studies of propranolol, verapamil and captopril. J Pharm Sci, 95(1), 37-44.
6. Dey, P., Maiti, S., 2010. Orodispersible tablets: A new trend in drug delivery. J Nat Sc Biol Med, 1(1), 2.
7. Genedy, S., Khames, A., Hussein, A., Sarhan, H., 2018. Hydralazine HCl rapidly disintegrating sublingual tablets: Simple dosage form of higher bioavailability and enhanced clinical efficacy for potential rapid control on hypertensive preeclampsia. Drug Des Devel Ther, 12, 3753.
8. Hua, S., 2019. Advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. Front Pharmacol, 10, 1328.

9. Hua, S.,2020. Advances in oral drug delivery for regional targeting in the gastrointestinal tract-influence of physiological, pathophysiological and pharmaceutical factors. Front Pharmacol, 11, 1-22.
10. Kumar, RS., Chandra, TS., 2019. Sublingual drug delivery systems-faster therapeutic action dosage forms. J Drug Deliv Ther, 9(4-A), 838-841.
11. Labhade, S., Malode, C., Rawal, V., Rupvate, S., 2019. Review on sublingual drug delivery system. J Drug Deliv Ther, 9(3), 684-688.
12. Londhe, V., Shirsat, R., 2018. Formulation and characterization of fast-dissolving sublingual film of iloperidone using Box–Behnken design for enhancement of oral bioavailability. AAPS PharmSciTech, 19(3), 1392-1400.
13. Madibone, MN., Gaikwad, SS., Nikam, VK., 2018. A review on sublingual route is themost promising choice in an emergency. Appl Clin Res Clin Trials Regul Aff, 5(3), 200-215.
14. Mathur, P., Rana, A., Saroha, K., Mathur, K., 2019. Sublingual route: an approach to administered drugs in systemic circulation. Int J Pharma Res Heal Sci, 7, 2869-2873.
15. Mayet-Cruz, L., Rodríguez, JM., Jung-Cook, H., 2021. Development of a dissolution test for melatonin sublingual tablets using a factorial experimental design. Farmacia, 69(1), 169-173.
16. Mohammadzadeh, R., Javadzadeh, Y., 2018. An overview on oral drug delivery via nano-based formulations. Pharm Biomed Res, 4(1), 1-7.
17. Muñoz-Wolf, N., Rial, A., Saavedra, JM., Chabalgoity, JA., 2014. Sublingual Immunotherapy as an alternative to induce protection against acute respiratory infections. J Vis Exp,90, 1-11.
18. Narang, N., Sharma, J., 2011. Sublingual mucosa as a route for systemic drug delivery. Int J Pharm Pharm Sci, 3(Suppl 2), 18-22.
19. Sevinç-Özakar, R., Özakar, E., 2021. Current overview of oral thin films. Turk J Pharm Sci, 18(1), 111.
20. Patel, P., Makwana, S., Jobanputra, U., Ravat, M., Ajmera, A., Patel, M., 2011. Sublingual route for the systemic delivery of Ondansetron. Int J Drug Dev Res, 3, 36-44.
21. Patel, VF., Liu, F., Brown, MB., 2012. Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug delivery systems. J Control Release, 161(3), 746-756.
22. Pawar, PP., Ghorpade, HS., Kokane, BA., 2018. Sublingual route for systemic drug delivery. J Drug Deliv Ther, 8(6-s), 340-343.
23. Pinto, S., Pintado, ME., Sarmento, B., 2020. In vivo, ex vivo and in vitro assessment of buccal permeation of drugs from delivery systems. Expert Opin Drug Deliv, 33-48.
24. Prajapati, ST., Patel, PB., Patel, CN., 2012. Formulation and evaluation of sublingual tablets containing Sumatriptan succinate. Int J PharmInvestig, 2(3), 162.
25. Sattar, M., Sayed, OM., Lane, ME., 2014. Oral transmucosal drug delivery–current status and future prospects. Int J Pharm, 471(1-2), 498-506.
26. Sheu, MT., Hsieh, CM., Chen, RN., Chou, PY., Ho, HO., 2016. Rapid-onset sildenafil sublingual drug delivery systems: In vitro evaluation and in vivo pharmacokinetic studies in rabbits. J Pharm Sci, 105(9), 2774-2781.
27. Şenel, S., Comoglu, T., 2018. Orally disintegrating tablets, fast-dissolving, buccal and sublingual formulations. Pharm Dev Technol, 23(5), 431-431,
28. Thirion-Delalande, C., Gervais, F., Fisch, C., Cuiné, J., Baron-Bodo, V., Moingeon, P., Mascarell, L., 2017. Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products. PLoS One, 12(9), e0183398.
29. Verma, H., Verma, S., Prasad, SB., Singh, H., 2014. Sublingual delivery of Frovatriptan: An indication of potential alternative route. Int Sch Res Notices, 2014, 1-9.
30. Yadav, N., 2015. Design, development, and evaluation of terbutaline sulfate sublingual tablets. Asian J Pharm, 9(3), 162-170.
31. Yoo, SD., Yoon, BM., Lee, HS., Lee, KC., 1999. Increased bioavailability of clomipramine after sublingual administration in rats. J Pharm Sci, 88(11), 1119-1121.