DEVELOPMENT OF BESIFLOXACIN HCL LOADED OCULAR IN SITU GELS; IN VITRO CHARACTERIZATION STUDY

Yıl 2023, Cilt: 47 Sayı: 1, 39 - 50, 20.01.2023

Heybet Kerem Polat Sedat Ünal

https://doi.org/10.33483/jfpau.1154051

Cited By: 1

Öz

Objective: The aim of this study is to develop in situ gel formulations containing besifloxacin hydrochloride are heat triggered, which are prepared by using different poloxamer and derivatives different polymers that will change the gelling temperature to increase corneal contact time, regulate drug release, improve ocular bioavailability and increase patient compliance increase mucoadhesion.

Material and Method: Various concentrations of poloxamer 188 (P188) and poloxamer 407 (P407) were used to create the in situ forming gels. To increase the gel's capacity for bioadhesion, mucoadhesives such hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were included in the formulations. Drug release in vitro, sol-gel transition temperature, rheological behavior, pH, clarity, and mucoadhesion force were all assessed for the produced formulations.

Result and Discussion: The developed formulations' gelation temperatures ranged from 29 to 35°C. The preparations' viscosity and mucoadhesion force increased with increasing P407, HPMC, and HEC concentrations. Besifloxacin HCl forms in situ gel formulas with K1, K2, K3, and K6 suited for mucoadhesion characteristics, gelation temperature, and viscosity. These formulations exhibit pseudoplastic flow. Increasing polymer concentrations resulted in a reduction in the burst release of the formulations. However, at the end of 6 hours, drug release was finished in all formulations. The results show that in situ gels containing P407 and P188 show promise for besifloxacin HCl application.

Anahtar Kelimeler

Besifloxacin HCl, gel, in situ, ocular, poloxamer

BESİFLOKSASİN HCL YÜKLÜ OKÜLER İN SİTU JELLERİN GELİŞTİRİLMESİ; İN VİTRO KARAKTERİZASYON ÇALIŞMASI

Öz

Amaç: Bu çalışmanın amacı, kornea temas süresi artırılmış, ilaç salımı düzenlenmiş, oküler biyoyararlanımı iyileştirilmiş ve hasta uyuncunu artırmak amacıyla jelleşme sıcaklığını değiştirecek farklı poloksomer türevlerinin ve mukoadhezyonu değiştirecek farklı polimerlerin kullanılması ile hazırlanan ısı ile tetiklenip jelleşen ve besifloksasin hidroklorür içeren in situ jel formülasyonları geliştirmektir.

Gereç ve Yöntem: İn situ jeller oluşturmak için poloksamer 188 (P188) ve poloksamer 407 (P407)'nin farklı farklı konsantrasyonları denenmiş bununla beraber in situ jelin biyo-yapışkanlık özelliklerini artırmak amacıyla formülasyonlara hidroksipropilmetil selüloz (HPMC) veya hidroksietil selüloz (HEC) gibi muko yapışkanlar ilave edilmiştir. Üretilen formülasyonların in vitro ilaç salımı, sol-jel geçiş sıcaklığı, reolojik davranışları, pH, berraklık ve mukoadezif kuvveti değerlendirilmiştir.

Sonuç ve Tartışma: Geliştirilen formülasyonların jelleşme sıcaklıkları 29 ila 35°C arasında olduğu belirlenmiştir. Preparatların viskozitesi ve mukoadezyon kuvveti, artan P407, HPMC ve HEC konsantrasyonları ile artmış. Patlama salımında bir azalma ile sonuçlanmıştır. Bununla beraber 6 saat sonunda bütün formülasyonlarda ilaç salımı bitmiştir. Jelleşme sıcaklığı, viskoziteleri ve mukoadhezyonları uygun olduğu için K1, K2, K3 ve K6 formülasyonları seçilmiş ve bu formülasyonlara besifloksasin HCl yüklenmiştir. Bu dört formülasyonun psödoplastik akış sergilediği tespit edilmiştir. Artan polimer konsantrasyonlarında formülasyonların patlama salımında bir azalma ile sonuçlanmıştır. Bununla beraber 6 saat sonunda bütün formülasyonlarda ilaç salımı bitmiştir. Sonuçlar, besifloksasin HCl uygulaması için P407 ve P188 içeren in situ jellerin umut vadettiğini göstermektedir.

Anahtar Kelimeler

Besifloksasin HCl, in situ, jel, oküler, poloksamer

Kaynakça

• 1. Lin, H.R., Sung, K.C. (2000). Carbopol/pluronic phase change solutions for ophthalmic drug delivery. Journal of Controlled Release, 69(3), 379-388. [CrossRef]
• 2. Blondeau, J.M. (2004). Fluoroquinolones: mechanism of action, classification, and development of resistance. Survey of Ophthalmology, 49(2), S73-S78. [CrossRef]
• 3. Polat, H.K., Pehlivan, S., Özkul, C., Çalamak, S., Öztürk, N., Aytekin, E., Fırat, A., Ulubayram, K., Kocabeyoğlu, S., Irkeç, M., Çalış, S. (2020). Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation. International Journal of Pharmaceutics, 585, 119552. [CrossRef]
• 4. Miller, D. (2013). Pharmacological treatment for infectious corneal ulcers. Expert Opinion on Pharmacotherapy, 14(5), 543-560. [CrossRef]
• 5. Polat, H.K. (2022). Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. Journal of Oral Biology and Craniofacial Research, 26(5), 1230-1241. [CrossRef]
• 6. Lee, V.H. (1990). New directions in the optimization of ocular drug delivery. Journal of Ocular Pharmacology and Therapeutics, 6(2), 157-164. [CrossRef]
• 7. Polat, H.K. In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. Journal of Research in Pharmacy, 26(4), 873-883. [CrossRef]
• 8. Miyazaki, S., Yokouchi, C., Nakamura, T., Hashiguchi, N., Hou, W.M., Takada, M. (1986). Pluronic F-127 gels as a novel vehicle for rectal administration of indomethacin. Chemical and Pharmaceutical Bulletin, 34(4), 1801-1808. [CrossRef]
• 9. Morishita, M., Barichello, J.M., Takayama, K., Chiba, Y., Tokiwa, S., Nagai, T. (2001). Pluronic® F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin. International Journal of Pharmaceutics, 212(2), 289-293. [CrossRef]
• 10. Dumortier, G., Grossiord, J.L., Agnely, F., Chaumeil, J.C. (2006). A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical Research, 23(12), 2709-2728. [CrossRef]
• 11. Chu, J.S., Amidon, G.L., Weiner, N.D., Goldberg, A.H. (1991). Mixture experimental design in the development of a mucoadhesive gel formulation. Pharmaceutical Research, 8(11), 1401-1407. [CrossRef]
• 12. Jones, D.S., Woolfson, A.D., Djokic, J., Coulter, W.A. (1996). Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharmaceutical Research, 13(11), 1734-1738. [CrossRef]
• 13. Morsi, N., Ghorab, D., Refai, H., Teba, H. (2016). Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery. International Journal of Pharmaceutics, 506(1-2), 57-67. [CrossRef]
• 14. Gugleva, V., Titeva, S., Ermenlieva, N., Tsibranska, S., Tcholakova, S., Rangelov, S., Momekova, D. (2020). Development and evaluation of doxycycline niosomal thermoresponsive in situ gel for ophthalmic delivery. International Journal of Pharmaceutics, 591, 120010[CrossRef]
• 15. Schmolka, I.R. (1972). Artificial skin I. Preparation and properties of pluronic F‐127 gels for treatment of burns. Journal of Biomedical Materials Research, 6(6), 571-582. [CrossRef]
• 16. Ribeiro A, Figueiras A, Santos D, Veiga F. (2008). Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin. AAPS PharmsciTech, 9, 1102-1109. [CrossRef]
• 17. Qi, H., Chen, W., Huang, C., Li, L., Chen, C., Li, W., Wu, C. (2007). Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. International Journal of Pharmaceutics, 337(1-2), 178-187. [CrossRef]
• 18. Singh, C.L., Singh, A., Kumar, S., Kumar, M., Sharma, P.K., Majumdar, D.K. (2015). Development and validation of different ultraviolet-spectrophotometric methods for the estimation of besifloxacin in different simulated body fluids. Indian Journal of Pharmaceutical Sciences, 77(4), 399. [CrossRef]
• 19. Karataş, A., Sonakin, O., Kiliçarslan, M., Baykara, T. (2009). Poly (ε-caprolactone) microparticles containing levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics. Journal of Microencapsulation, 26(1), 63-74. [CrossRef]
• 20. Thakor, S., Vhora, I., Desai, J., Thakkar, S., Thakkar, H. (2012). Physiologically activated phase transition systems for improved ocular retention of ketorolac tromethamine. Journal of Pharmacy Bioallied Sciences, 4(Suppl 1), S6. [CrossRef]
• 21. Patel, A., Cholkar, K., Agrahari, V., Mitra, A.K. (2013). Ocular drug delivery systems: An overview. World Journal of Pharmacology, 2(2), 47-64. [CrossRef]
• 22. Pawar, P., Katara, R., Mishra, S., Majumdar, D.K. (2013). Topical ocular delivery of fluoroquinolones. Expert Opinion on Drug Delivery, 10(5), 691-711. [CrossRef]
• 23. Abd Elhady, S.S., Mortada, N.D., Awad, G.A., Zaki, N.M. (2003). Development of in situ gelling and muco adhesive mebeverine hydrochloride solution for rectal administration. Saudi Pharmaceutical Journal, 11. [CrossRef]
• 24. Gilbert, J.C., Richardson, J.L., Davies, M.C., Palin, K.J., Hadgraft, J. (1987). The effect of solutes and polymers on the gelation properties of pluronic F-127 solutions for controlled drug delivery. Journal of Controlled Release, 5(2), 113-118. [CrossRef]
• 25. Shaikh, R., Singh, T.R.R., Garland, M.J., Woolfson, A.D., Donnelly, R.F. (2011). Mucoadhesive drug delivery systems. Journal of Pharmacy and Bioallied Sciences, 3(1), 89-100. [CrossRef]
• 26. Dantas, M.G.B., Reis, S.A.G.B., Damasceno, C.M.D., Rolim, L.A., Rolim-Neto, P.J., Carvalho, F.O., Almeida, J.R.G.D.S. (2016). Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Scientific World Journal, 2016, 7394685. [CrossRef]
• 27. Fathalla, Z.M., Vangala, A., Longman, M., Khaled, K.A., Hussein, A.K., El-Garhy, O.H., Alany, R.G. (2017). Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies. European Journal of Pharmaceutics and Biopharmaceutics, 114, 119-134. [CrossRef]
• 28. Okur, N., Yozgatli, V., Okur, M.E. (2020). In vitro–in vivo evaluation of tetrahydrozoline‐loaded ocular in situ gels on rabbits for allergic conjunctivitis management. Drug Development Research, 81(6), 716-727. [CrossRef]
• 29. Kurniawansyah, I.S., Rusdiana, T., Sopyan, I., Ramoko, H., Wahab, H.A., Subarnas, A. (2020). In situ ophthalmic gel forming systems of poloxamer 407 and hydroxypropyl methyl cellulose mixtures for sustained ocular delivery of chloramphenicole: Optimization study by factorial design. Heliyon, 6(11), e05365. [CrossRef]
• 30. Alexandridis, P., Hatton, T.A. (1995). Poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 96(1-2), 1-46. [CrossRef]
• 31. El-Kamel, A.H. (2002). In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International Journal of Pharmaceutics, 241(1), 47-55. [CrossRef]
• 32. Srivastava, M., Kohli, K., Ali, M. (2016). Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Delivery, 23(1), 154-166. [CrossRef]
• 33. Öztürk Atar, K. (2022). Development and in-vitro characterization of 1-cysteine loaded alginate beads for oral delivery. Journal of Research In Pharmacy, 26(1), 210-218. [CrossRef]
• 34. Ashrafi, H., Azadi, A. (2016). Chitosan-based hydrogel nanoparticle amazing behaviors during transmission electron microscopy. International Journal of Biological Macromolecules, 84, 31-34. [CrossRef]
• 35. Jafari-Aghdam, N., Adibkia, K., Payab, S., Barzegar-Jalali, M., Parvizpur, A., Mohammadi, G., Sabzevari, A. (2016). Methylprednisolone acetate–Eudragit® RS100 electrospuns: Preparation and physicochemical characterization. Artificial cells, Nanomedicine, and Biotechnology, 44(2), 497-503. [CrossRef]