Neslihan ÜSTÜNDAĞ OKUR
(İstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalı, İstanbul, Türkiye)
Ayşegül YOLTAŞ
(Ege Üniversitesi, Fen Fakültesi, Biyoloji Bölümü, Temel ve Endüstriyel Mikrobiyoloji Anabilim Dalı, İzmir, Türkiye)
Vildan YOZGATLI
(İstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalı, İstanbul, Türkiye)
Yıl: 2016Cilt: 13Sayı: 3ISSN: 1304-530X / 2148-6247Sayfa Aralığı: 311 - 317İngilizce

102 0
Development and Characterization of Voriconazole Loaded In Situ Gel Formulations for Ophthalmic Application
The aim of the this research was to prepare and evaluate the potential use of in situ gel formulations for ocular delivery of voriconazole for the treatment of fungal keratitis. An in situ gelling system was used to increase the residence time and thus the bioavailability of voriconazole in ocular mucosa. Temperature triggered in situ gel formulations were prepared by cold method using polymers like poloxamer 188, poloxamer 407 and sodium alginate. Finally, concentration of voriconazole in formulations was 0.1% (w/w). These formulations were evaluated for clarity, sol-gel transition temperature, gelling capacity, pH, viscosity and drug content. The gelation temperatures of all the formulations were within the range of 32-34°C. All the formulations exhibited fairly uniform drug content. Furthermore in vitro drug release and antifungal activity of these formulations were also evaluated. Drug release study of all the formulations showed sustained release properties. In conclusion, voriconazole loaded in situ gels could be offered as a promising strategy for ocular drug delivery for the treatment of fungal keratitis.
DergiAraştırma MakalesiErişime Açık
  • 1. Almeida H, Amaral MH, Lobão P, Lobo JM. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discov Today 19, 400-412, 2014.
  • 2. Üstündağ-Okur N, Homan-Gökçe E. Lipid nanoparticles for ocular drug delivery. Int J Ophthalmic Res 1(3), 77-82, 2015.
  • 3. Makwana SB, Patel VA, Parmar SJ. Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results Pharma Sci, doi:10.1016/j.rinphs.2015.06.001, 2015.
  • 4. Üstündağ-Okur N, Gökçe EH, Boybıyık DI, Eğrilmez S, Ertan G, Özer Ö. Novel nanostructured lipid carrier based inserts for controlled ocular drug delivery: Evaluation of corneal bioavailability and treatment efficacy on bacterial keratitis. Expert Opin Drug Deliv 12(11), 1-17, 2015.
  • 5. Üstündağ-Okur N, Gökçe EH, Eğrilmez S, Özer Ö, Ertan G. Novel ofloxacin-loaded microemulsion formulations for ocular delivery. J Ocul Pharmacol Ther 30(4), 319-332, 2014.
  • 6. Swapnil D, Sonawane, Lahoti S. Design and evaluation of ion induced in situ gel formulation for levofloxacin hemihydrateocular delivery. Int J Pharm Sci Invent 3, 38-43, 2014.
  • 7. Darwhekar G, Jain P, Jain DK, Agrawal G. Development and optimization of dorzolamide hydrochloride and timolol maleate in situ gel for glaucoma treatment. Asian J Pharm 1, 93-97, 2011.
  • 8. Jung JH, Abou-Jaoude M, Carbia BE, Plummer C, Chauhan A. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone hydrogel contact lenses. J Control Release 165, 82– 89, 2013.
  • 9. Gallarate M, Chirio D, Bussano R, Peira E, Battaglia L, Baratta F, Trotta M. Development of O/W nanoemulsions for ophthalmic administration of timolol. Int J Pharm 440, 126-134, 2013.
  • 10. Mandal S, Thimmasetty MKMJ, Geetha MS. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharm Investig 2(2), 78-82, 2012. 11. Hosny KM. Preparation and evaluation of thermosen sitive liposomal hydrogel for enhanced transcorneal permeation of ofloxacin. AAPS PharmSciTech 10, 1336-1342, 2009.
  • 12. Hosny KM, Hassan AH. Intranasal in situ gel loaded with saquinavir mesylate nanosized microemulsion: Preparation, characterization, and in vivo evaluation. Int J Pharm 475(1-2), 191-197, 2014.
  • 13. Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. TODDJ 2, 61-67, 2008.
  • 14. Garala K, Joshi P, Patel J. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig 3, 29-41, 2013.
  • 15. Moemen D, Bedir T, Awad EA, Ellayeh A. Fungal keratitis: Rapid diagnosis using methylene blue stain. EJBAS doi:10.1016/j. ejbas.2015.08.001, 2015.
  • 16. Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf B Biointerfaces 117, 82–88, 2014.
  • 17. Qian Y, Wang F, Li R, Zhang Q, Xu Q. Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide. Drug Dev Ind Pharm 36(11), 1340-1347, 2010.
  • 18. Efron N, Young G, Brennan NA. Ocular surface temperature. Curr Eye Res 8, 901-906, 1989.
  • 19. Rathore KS, Nema RK, Sisodia SS. Preparation and characterization of timolol maleate ocular films. J Pharm Tech Res 2(3), 1995-2000, 2010. 20. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard CLSI document M38-A2. Clinical and Laboratory Standards Institute, Wayne, PA, 2008.
  • 21. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved Standard M27-A3. Clinical Laboratory Standards Institute Wayne, PA. 2009.
  • 22. Ansari Z, Miller D, Galor A. Current thoughts in fungal keratitis: diagnosis and treatment. Curr Fungal Infect Rep 7, 209-218, 2013.
  • 23. Shukla SH, Kumar M, Keshava GBS. Mycotic keratitis: an overview of diagnosis and therapy. Mycoses 51, 183-199, 2008.
  • 24. Borole PM, Chaudhari YS, Dharashivkar SS, Kumavat SD, Shenghani K, Shah PR. Preparation and evaluation of in situ gel of levofloxacin hemihydrate for treatment of peridontal disease. IJPRBS 2(3), 185-196, 2013.
  • 25. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics. Pharm Res 23, 2709-2728, 2006.
  • 26. Gonnering R, Edelhauser HF, Van Horn DL, Durant W. The pH tolerance of rabbit and human corneal endothelium. Invest Ophthalmol 18, 37- 390, 1979.
  • 27. Üstündağ-Okur N, Gökçe EH, Boybıyık DI, Eğrilmez S, Özer Ö, Ertan G. Preparation and in vitro–in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis, Eur J Pharm Sci 2014; 63: 204-215.
  • 28. Mandal S, Thimmasetty MKMJ, Prabhushankar GL, Geetha MS. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharm Investig 2(2), 78-82, 2012.
  • 29. Espinel-Ingroff A, Johnson E, Hockey H, Troke P. Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies. J Antimicrob Chemother 61, 616-620, 2008.
  • 30. Araujo R, Pina-Vaz C, Rodrigues AG. Susceptibility of environmental versus clinical strains of pathogenic Aspergillus. Int J Antimicrob Agents 29, 108-111, 2007.
  • 31. Arikan S, Sancak B, Alp S, Hascelik G, Mcnicholas P. Comparative in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against Aspergillus and Rhizopus, and synergy testing for Rhizopus. Med Mycol 46, 567-573, 2008.
  • 32. Pfaller MA, Diekema DJ, Rinaldi MG, Barnes R, Hu B, Veselov AV, Tiraboschi N, Nagy E, Gibbs DL. Results from the ARTEMIS DISK global antifungal surveillance study: a 6.5-year analysis of susceptibilities of candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing. J Clin Microbiol 43(12), 5848-5859, 2005.

TÜBİTAK ULAKBİM Ulusal Akademik Ağ ve Bilgi Merkezi Cahit Arf Bilgi Merkezi © 2019 Tüm Hakları Saklıdır.