OPHTHALMIC IN-SITU SUSTAINED GEL OF CIPROFLOXACIN, PREPARATION AND EVALUATION STUDY
Keywords:Ophthalmic in-situ gel, Poloxamer, Ciprofloxacin HCl, Solution-gel transition
Objective: This work aims to formulate and evaluate an ophthalmic in-situ gel of ciprofloxacin hydrochloride (HCl) using poloxamer 407 (P407) as a gelling agent and hydroxypropyl methylcellulose (HPMC) as a viscosity modifier. The objective of this work was to prolong the contact time as the in-situ gel will be converted into a gel upon contact with the cul-de-sac.
Methods: Ciprofloxacin HCl ophthalmic in-situ gel was prepared by utilizing (P407) as a temperature-dependent polymer while hydroxypropyl methylcellulose was used as a viscosity modifier. The system was evaluated for physical appearance, pH, drug content, sterility, irritancy and stability. In addition, gelation temperature and a viscosity at different shear rates and different temperatures were studied. The compatibility of the polymer with ciprofloxacin was studied by using fourier transform infrared spectroscopy (FTIR). The in vitro release of the drug was also evaluated and supported by a preliminary in vivo test.
Results: The results showed that the prepared formulas were clear, with acceptable pH and the drug contents were within the acceptable limits. FTIR results detected no incompatibility between poloxamer 407 and ciprofloxacin HCl. Notably, the viscosity of the system showed a pseudoplastic behaviour where a reduction in viscosity upon increasing the shear rate was observed. The in vitro release study confirmed the prolongation of the release of the optimized formula (F6) up to 8 h. Upon application of F6 into eyes of rabbits there was no irritancy. In addition, in vivo elimination study showed a prolonged contact for the in-situ gel in comparison with the rapid clearance of eye drop. Stability study indicated the stability of the optimized formula (F6).
Conclusion: The prepared optimized formula (F6) represents a successful, safe, stable and prolonged release in-situ gel formula of ciprofloxacin.
Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 2005;57:1595â€“639.
Almeida H, Amaral MH, LobÃ£o P, Lobo JMS. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug Discovery Today 2014;19:400â€“12.
Shah JN. Formulation, optimization and characterization of novel controlled ophthalmic drug delivery systems of some fluoroquinolones. Ganpat University; 2011.
Horvat G, Gyarmati B, Berko S, Szabo-Revesz P, Szilagyi BA, SzilÃ¡gyi A, et al. Thiolated poly(aspartic acid) as potential in situ gelling, ocular mucoadhesive drug delivery system. Eur J Pharm Sci 2015;67:1â€“11.
Morsi N, Ibrahim M, Refai H, El Sorogy H. Nanoemulsion-based electrolyte triggered in situ gel for ocular delivery of acetazolamide. Eur J Pharm Sci 2017;104:302â€“14.
Almeida H, Amaral MH, Lobao P SLJ. Applications of poloxamers in ophthalmic pharmaceutical formulations: an overview. Expert Opin Drug Delivery 2013;10:1223â€“37.
Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 2006;23:2709â€“28.
Abdelkader H, Mansour HF. Comparative studies for ciprofloxacin hydrochloride pre-formed gels and thermally triggered (in situ) gels: in vitro and in vivo appraisal using a bacterial keratitis model in rabbits. Pharm Dev Technol 2015;20:410â€“6.
BP British Pharmacopoeia. Stationary Office 2009; 2010. p. 5000.
Patel N, Thakkar V, Metalia V, Baldaniya L, Gandhi T, Gohel M. Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept. Drug Dev Ind Pharm 2016;42:1406â€“23.
Shashank Nayak N, Sogali BS, Thakur RS. Formulation and evaluation of pH-triggered in situ ophthalmic gel of Moxifloxacin hydrochloride. Int J Pharm Pharm Sci 2012;4:452â€“9.
Destruel PL, Zeng N, Maury M, Mignet N, Boudy V. In vitro and in vivo evaluation of in situ gelling systems for sustained topical ophthalmic delivery: state of the art and beyond. Drug Discovery Today 2017;22:638â€“51.
Almeida H, Lobao P, Frigerio C, Fonseca J, Silva R, Quaresma P, et al. Development of mucoadhesive and thermosensitive eyedrops to improve the ophthalmic bioavailability of ibuprofen. J Drug Delivery Sci Technol 2016;35:69â€“80.
Rathore KS. In-situ gelling ophthalmic drug delivery system: an overview. Int J Pharm Pharm Sci 2010;2:30â€“4.
Lin HR, Sung KC. Carbopol/pluronic phase change solutions for ophthalmic drug delivery. J Controlled Release 2000;69:379â€“88.
Allah AKA, Hammid SNA. Preparation and evaluation of chloramphenicol as a thermosensitive ocular in-situ gel. Iraqi J Pharm Sci 2012;21:98-105.
El-Laithy HM, Nesseem DI, El-Adly AA, Shoukry M. Moxifloxacin-gelrite in situ ophthalmic gelling systems against photodynamic therapy for treatment of bacterial corneal inflammation. Arch Pharm Res 2011;34:1663â€“78.
Deshpande J, Shah PB, Bhandari A. Design and development of pH-monitered in situ gel of Lomefloxacin. J Pharm Sci Biosci Res 2013;3:10â€“5.
USP 32 NF 27. 32nd ed. United States Pharmacopeial Convention; 2009.
MA Fathalla Z, Vangala A, Longman M, Khaled KA, Hussein AK, El-Garhy OH, et al. Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: design, characterisation, toxicity and transcorneal permeation studies. Eur J Pharm Biopharm 2017;114:119â€“34.
Galgatte UC, Chaudhari PD. Preformulation study of poloxamer 407 gels: effect of additives. Int J Pharm Pharm Sci 2014;6:130â€“3.
Cao F, Zhang X, Ping Q. New method for ophthalmic delivery of azithromycin by poloxamer/carbopol-based in situ gelling system. Drug Delivery 2010;17:500â€“7.
Sheshala R, Quah SY, Tan GC, Meka VS, Jnanendrappa N, Sahu PS. Investigation on a solution-to-gel characteristic of thermosensitive and mucoadhesive biopolymers for the development of moxifloxacin-loaded sustained release periodontal in situ gels. Drug Delivery Transl Res 2018;1:1â€“10.
Park E, Song K. Rheological properties of poloxamer 407 solutions and gels. Annu Trans Nord Rheol Soc 2011;19:1â€“5.
Wu H, Liu Z, Peng J, Li L, Li N, Li J, et al. Design and evaluation of baicalin-containing in situ pH-triggered gelling system for sustained ophthalmic drug delivery. Int J Pharm 2011;410:31â€“40.
Mansour M, Mansour S, Mortada ND, Abd ElHady SS. Ocular poloxamer-based ciprofloxacin hydrochloride in situ forming gels. Drug Dev Ind Pharm 2008;34:744â€“52.
Abou el Ela AESF, Khatib MM El. Formulation and evaluation of new long-acting metoprolol tartrate ophthalmic gels. Saudi Pharm J 2014;22:555â€“63.
Lihong W, Xin C, Yongxue G, Yiying B, Gang C. Thermoresponsive ophthalmic poloxamer/tween/carbopol in situ gels of a poorly water-soluble drug fluconazole: preparation and in vitro-in vivo evaluation. Drug Dev Ind Pharm 2014;40:1402â€“10.
Bachhav HD, Savkare A, Karmarkar R, Derle D. Development of poloxamer-based thermosensitive in situ ocular gel of betaxolol hydrochloride. Int J Pharm Pharm Sci 2015;7:4â€“8.
Paradkar MU, Parmar M. Formulation development and evaluation of natamycin niosomal in-situ gel for ophthalmic drug delivery. J Drug Delivery Sci Technol 2017;39:113â€“22.
Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. Open Drug Delivery J 2008;2:61â€“70.
Dewan M, Sarkar G, Bhowmik M, Das B. Effect of gellan gum on the thermogelation property and drug release profile of Poloxamer 407 based ophthalmic formulation. Int J Biol Macromol 2017;102:258â€“65.
Bhowmik M, Kumari P, Sarkar G, Kanti M, Bhowmick B, Bhattacharjee D, et al. Effect of xanthan gum and guar gum on in situ gelling ophthalmic drug delivery system based on poloxamer-407. Int J Biol Macromol 2013;62:117â€“23.
Alexandridis P, Hatton TA. Poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids Surfaces 1995;7757:1â€“46.
Asasutjarit R, Thanasanchokpibull S, Fuongfuchat A, Veeranondha S. Optimization and evaluation of thermo-responsive diclofenac sodium ophthalmic in situ gels. Int J Pharm 2011;411:128â€“35.
Song J, Bi H, Xie X, Guo J, Wang X, Liu D. Preparation and evaluation of sinomenine hydrochloride in situ gel for uveitis treatment. Int Immunopharmacol 2013;17:99â€“107.