OPTIMIZATION AND CHARACTERIZATION OF ION ACTIVATED OCULAR IN-SITU GEL FORMULATION FOR BACTERIAL CONJUNCTIVITIS

  • ANKITA KAPOOR ISF College of Pharmacy Moga, Affiliated to I. K. Gujral Punjab Technical University, Jalandhar
  • G. D. GUPTA ISF College of Pharmacy Moga, Affiliated to I. K. Gujral Punjab Technical University, Jalandhar

Abstract

Objective: The present research work aims at describing the formulation, optimization and evaluation of ion activated ocular in-situ gel of gatifloxacin for treatment of bacterial conjunctivitis so as to overcome patient inconvenience, precorneal drug elimination, variation in efficacy, vision blurring and frequent instillation associated with conventional eye drops and ointments.


Methods: In-situ gel was prepared using gellan gum as an ion activated phase transition polymer and HPMC K100M as release retardant. Gatifloxacin was characterized by spectrophotometry. Crystalline state of the drug was determined using X Ray Diffraction study. The developed formulation exhibited instantaneous gel formation in simulated lacrimal fluid (pH 7.4), which was further evaluated for its rheology, irritancy parameters, in vitro release, trans-corneal permeation and antimicrobial activity.


Results: Gatifloxacin exhibited λmax 286 nm obeying Beer Lambert’s law and pH-dependent solubility at a pH range of 2 to 4. 0.6% gellan gum and 0.4% HPMC K100M were optimized in the formulation which exhibited a viscosity of 55 cps in sol form and 325 cps in gel form with pseudoplastic behavior and prolonged in vitro release. Permeation of formulation was 75.8% in 7 h with log P of drug 0.59. Developed isotonic and non-irritant formulation had a lower apparent permeability coefficient of 8.15 x 10-5 cm/sec as compared to marketed formulation.


Conclusion: A Formulation can be viewed as an efficacious medicine by virtue of its higher zone of inhibition, ability to enhance precorneal residence time and consequently ocular bioavailability with lesser frequency of administration attributed to slow and prolonged diffusion of the drug from the polymeric solutions.

Keywords: Gatifloxacin, In-situ, Pseudo plastic, Pre-corneal Residence, Isotonic, Rheology, On activated

References

1. Morrow GL, Richard L. Conjunctivitis. Am Fam Physician 1998;57 Suppl 4:735-46.
2. Leung AKC, Hon KL, Wong AHC, Wong AS. Bacterial conjunctivitis in childhood: etiology, clinical manifestations, diagnosis, and management. Recent Pat Inflamm Allergy Drug Discovery 2018;12 Suppl 2:120-7.
3. Pichichero ME. Bacterial conjunctivitis in children: antibacterial treatment options in an era of increasing drug resistance. Clin Pediatr (Phila) 2011;50 Suppl 1:7-13.
4. Epling J, Smucny J. Bacterial conjunctivitis. Clin Evid 2005;2 Suppl 14:756-61.
5. Kristiina J, Tomi J, Urtii A. Ocular absorption following drug delivery. Adv Drug Delivery Rev 1995;16:3-19.
6. Sreeraj M, Mitra AK, Hughes PM. In ophthalmic drug delivery systems. Marcel Deckker, Inc., Kanas city, Missouri, U. S. A.; 2003. p. 1-5.
7. Balasubramaniam J, Pandit JK. Ion-activated in-situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride. Drug Delivery 2003;10:185-91.
8. Schoenwald RD, Ward RL, Desantis LM, Rochrs RE. Influence of high viscosity vehicles on miotic effect of pilocarpine. J Pharm Sci 1978;67:1280-4.
9. Maurice DM, Srinivas SD. Use of flourimetry in assessing the efficacy of a cation sensitive gel as an ophthalmic vehicle; comparison with scintigraphy. J Pharm Sci 1992;81:615-9.
10. Mishra DN, Gilhotra RM. Design and characterization of bioadhesive in-situ gelling ocular inserts of gatifloxacin sesquihydrate. DARU 2008;16:1-7.
11. Nanjawade BK, Manvi FV, Manjappa AS. In-situ-forming hydrogels for sustained ophthalmic drug delivery. J Controlled Release 2007;122:119-34.
12. Bolanle L. Development of a cysteamine in-situ gelling system for the treatment of corneal crystals in cystinosis. University of London, London; 2008.
13. Gurny R. Preliminary studies of porlonged acting drug delivery system for the treatment of glaucoma. Pharm Acta Helv 1981;56:130-2.
14. Naseem AC, Kohli K, Ali A. Preparation of in-situ froming ophthalmic gels of ciprofloxacin hydrochloride for the treatment of bacterial conjunctivitis: in vitro and in vivo studies. J Pharm Sci 2002;92:407-13.
15. Sultana Y, Aquil M, Ali D, Zafar S. Evaluation of carbopol-methyl cellulose-based sustained-release ocular delivery system for pefloxacin mesylate using rabbit eye model. Pharm Dev Technol 2006;11:313-9.
16. Srividya B, Rita M, Cardoza RM, Amin PD. Sustained ophthalmic delivery of ofloxacin from a pH triggered in-situ gelling system. J Controlled Release 2001;73:205-11.
17. Mansour M, Mansour S, Mortada ND, Abd Elhady SS. Ocular poloxamer-based ciprofloxacin hydrochloride in-situ forming gels. Drug Dev Ind Pharm 2008;34:744-52.
18. Ma WD, Xu H, Wang C, Nie SF, Pan WS. Pluronic F127-g-poly(acrylic acid) copolymers as in-situ gelling vehicle for ophthalmic drug delivery system. Int J Pharm 2008;350:247-56.
19. Gupta H, Jain S, Mathur R, Mishra P, Mishra AK, Velpandian T. Sustained ocular drug delivery from temperature and pH triggered novel in-situ gel system. Drug Delivery 2007;14:507-15.
20. Vadnere M, Amidon G, Lendenbaum S, Haslam JL. Thermodynamic study on the gel-sol transition of some pluronic polyols. Int J Pharm 1984;22:207-18.
21. John C, Katarina E, Roger P, Katarina J. Rheological evaluation of Gelrite® in-situ gels for ophthalmic use. Eur J Pharm Sci 1998;6:113-9.
22. Balasubramaniam J, Pandit JK. Ion-activated in-situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride. Drug Delivery 2003;10:185-91.
23. Smadar C, Esther L, Amira T, Yael P. A novel in-situ-forming ophthalmic drug delivery system from alginates undergoing gelation in the eye. J Controlled Release 1997;44:201-8.
24. Venugopal K, Saha RN. New, simple and validated UV-spectrophotometric methods for the estimation of gatifloxacin in bulk and formulations. Farmaco 2005;60 Suppl 11-12:906-12.
25. Doijad RC, Manvi FV, Malleswara VSN, Aalse P. Sustained ophthalmic delivery of gatifloxacin from in-situ gelling system. Indian J Pharm Sci 2006;68 Suppl 6:814-8.
26. Indian Pharmacopoeia. The Indian Pharmacopoeia Commission, Govt of India. Ministry of health and family Welfare: Ghaziabad; 2007. p. 540.
27. Kalam MA, Sultana Y, Samad A, Ali A, Aquil M, Sharma M, et al. Gelrite based in vitro gelation ophthalmic drug delivery system of gatifloxacin. J Dispersion Sci Technol 2008;29:89-96.
28. Valerie N, Shlomit W, Greta S. Crystalline forms of gatifloxacin. US Patent 7,396,839 B2; 2008.
29. Boubarkar BB, Corinne A, Celine V, Arnaud C, Claudine Q. Activity of gatifloxacin in an in vitro pharmacokinetic-pharmacodynamic model against Staphylococcus aureus strains either susceptible to ciprofloxacin or exhibiting various levels and mechanisms of ciprofloxacin resistance. Antimicrob Agents Chemother 2006;50 Suppl 6:1931-6.
30. United States Pharmacopoeia-24 NF-19. The United State Pharmacopoeial Convention Incorporation: Rockville, M. D.; 2000. p. 10.
31. Kashyap N, Viswanad B, Sharma G, Bhardwaj V, Ramarao P, Kumar MNV. Design and evaluation of biodegradable, bio sensitive in-situ gelling systems for pulsatile delivery of insulin. Biomaterials 2007;28:2051–60.
32. Kurniawansyah IS, Sopyan I, Wathoni N, Fillah Dl, Praditya RU. Application and characterization of in-situ gel. Int J Appl Pharm 2018;10 Suppl 6:34-7.
33. Hurler J, Engesland A, Poorahmary B, Natasa K, Basnet S. Improved texture analysis of Hydrogel characterization: gel cohesiveness, adhesiveness and hardness. J Appl Polym Sci 2012;125 Suppl 1:180-8.
34. Gokulgandhi MR, Parikh JR, Barot M, Modi DM. A pH triggered in-situ gel forming ophthalmic drug delivery system for tropicamide. Drug Delivery Technol 2007;5:44-9.
35. Hiremath SSP, Dasankoppa FS, Nadaf A, Jamakandi VG. Formulation and evaluation of a novel in-situ gum-based ophthalmic drug delivery system of linezolid. Sci Pharm 2008;76:515-32.
36. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25–35.
37. Peppas NA. Analysis of Fickian and non-fickian drug release from polymers. Pharm Acta Helv 1985;60:110–1.
38. Laddha UD, Mahajan HS. An insight to ocular in-situ gelling systems. Int J Appl Pharm 2017;6 Suppl 2:31-40.
39. Rupenthal ID. Ocular delivery of antisense oligonucleotides using colloidal carriers: improving the wound repair after corneal surgery. PhD Thesis The University of Auckland, NewZealand.20; 2008.
40. Dabir PD, Shahi SR, Deore SV. Opthalmic in situ gel: a review. Eur J Pharm Med Res 2016;3:205-15.
41. Vinardell MP, Mitjans M. Alternative methods for eye and skin irritation tests: an overview. J Pharm Sci 2008;97:46-59.
Statistics
48 Views | 37 Downloads
Citatons
How to Cite
KAPOOR, A., & GUPTA, G. D. (2020). OPTIMIZATION AND CHARACTERIZATION OF ION ACTIVATED OCULAR IN-SITU GEL FORMULATION FOR BACTERIAL CONJUNCTIVITIS. International Journal of Applied Pharmaceutics, 12(4), 182-191. https://doi.org/10.22159/ijap.2020v12i4.37925
Section
Original Article(s)