PREPARATION AND IN VITRO EVALUATION OF NAPROXEN AS A pH SENSITIVE OCULAR IN-SITU GEL
Objective: The aim of this study was to prepare and evaluate a pH sensitive ocular in-situ gel of Naproxen, to increase the ocular residence time.
Methods: pH sensitive in situ gel formulations were prepared using different concentrations of Carbomer CB [0.5%, 0.6%, 0.7%] in combination with hydroxypropyl methylcellulose HPMC K40 [0.75%, 1%, 1.5%] or HPMC K100 [0.5%, 0.75%, 1%, 1.5%]. The prepared in situ gels were evaluated for appearance, pH, gelling capacity [sol-to-gel transition/in vitro], tonicity, viscosity, in vitro release studies, release kinetic analysis, and the selected formulas were subjected to rheological studies, and the finally selected formula was subjected to drug content, FT-IR studies, and ocular irritancy tests.
Results: Increasing the concentration of the carbomer polymer improved the gelling capacity and gelation time, also the higher the viscosity and concentration of the hydrophilic HPMC polymer, the higher the viscosity of the formula, which affected the release, gelation capacity and time. The overall results showed that formula F10 [CB 0.7%, HPMC K100 0.75%] exhibited excellent pH-triggered in-situ gelation time, sustained the release of naproxen for 3 h’ time with a release rate of more than 90%.
Conclusion: Ocular in situ gel of naproxen offers a potential dosage form to increase the residence time in the ocular cul de sac, decreasing the drug drainage, and increasing the effectiveness of the drug.
2. Kurniawansyah IS, Sopyan I, Wathondi N, Fillah DL, Praditya RU. Application and characterization of in situ gel. Int J Appl Pharm 2018;10:34–7.
3. Dholakia M, Dave R, Thakkar V, Rana H, Gohel M, Patel N. Newer ophthalmic in situ gel of moxifloxacin hydrochloride?: optimization using box behnken statistical design. Int J Pharm Pharm Sci 2018;10:5–13.
4. Conway B. Recent patents on ocular drug delivery systems. Recent Pat Drug Delivery Formulation 2008;2:1–8.
5. Tangri P, Khurana S. Basics of ocular drug delivery systems. Int J Res Pharm Biomed Sci 2011;2:1541–52.
6. Al-tahami K, Singh J. Smart polymer-based delivery systems for peptides and proteins. Recent Pat Drug Delivery Formulation 2007;1:65–71.
7. Sandeep D, Narayana Charyulu R, V AN. Smart in situ gels for glaucoma-an overview. Int J Pharm Sci Rev Res 2018;50:94–100.
8. Peneva PT. Non-steroidal anti-inflammatory drugs for topical ophthalmic administration: contemporary trends. Int J Pharm Pharm Sci 2015;7:13–9.
9. Russo P, PaPa V, Russo S, Bella A DI, Pabst G, Milazzo G, et al. Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: effect of sodium naproxen. Eur J Ophthalmol 2005;15:598-606.
10. Cherng Chyi RF, Lidgate DM. Ophthalmic NSAID formulations containing a quaternary ammonium preservative and a nonionic surfactant. Vol. 5,110,493, United States Patent. USA: Commission of Parents and Trademarks 5,110,493; 1992.
11. Megbelayin EO PS. Managing challenges of recalcitrant intra-operative miosis during small incision cataract surgery. Int J Sci Res Knowledge 2013;1:74–81.
12. Marques MRC, Loebenberg R, Almukainzi M. Simulated biological fluids with possible application in dissolution testing. Dissolution Technol 2011;18:15–28.
13. Dharmalingam SR, Ramamurthy S, Chidambaram K, Nadaraju S. Development and validation of UV spectrophotometric method for the estimation of naproxen in bulk and semi-solids formulation. Int J Anal Pharm Biomed Sci 2013;2:49–55.
14. Attia DA. In vitro and in vivo evaluation of transdermal absorption of naproxen sodium. Aust J Basic Appl Sci 2009;3:2154–65.
15. Parthiban KG, Manivannan R, Kumar BS, Ahasan MB. Formulation and evaluation of ketorolac ocular pH-triggered in-situ gel. Int J Drug Dev Res 2010;2:459–67.
16. Dabir PD, Shahi SR, Deore SV. Opthalmic in situ gel: a review. Eur J Pharm Med Res 2016;3:205–15.
17. Debnath SK, Sarkar S, Janakiraman K, Chakraborty S. Formulation and evaluation of aceclofenac gel. Int J ChemTech Res 2009;1:204–7.
18. Makwana SB, Patel VA, Parmar SJ. Development and characterization of in-situ gel for an ophthalmic formulation containing ciprofloxacin hydrochloride. Results Pharma Sci 2016;6:1–6.
19. Meshram S, Thorat S, Meshram S. Review article ocular in situ gels: development, evaluation and advancements. Sch Acad J Pharm 2015;4:340–6.
20. Rajesh A, A PN, Smit S, Sangeeta A, Ashok B. Sustain ophthalmic delivery of levofloxacin from a pH-triggered in-situ gelling system. Int Res J Pharm 2012;3:273–6.
21. Ali Allah AK, Abd-Al Hammid SN. Preparation and evaluation of chloramphenicol as a thermosensitive ocular in-situ gel. Iraqi J Pharm Sci 2012;21:98–105.
22. El-Laithya HM, Nesseem DI MS. Evaluation of two in-situ gelling systems for ocular delivery of moxifloxacin: in vitro and in vivo studies. J Chem Pharm Res 2011;3:66–79.
23. Jug M, Hafner A, Lovric J, Kregar ML, Pepic I, Vanic Z, et al. An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems. J Pharm Biomed Anal 2017;5:173–82.
24. Anshul S, Renu S. A review on levofloxacin in the situ-gel formulation. Asian J Pharm Clin Res 2015;8:37–41.
25. Kumar A, Tiwari BK, Kumar S. Evaluation of ocular films of ofloxacin for antibacterial activity. Int J Appl Pharm 2018;10:275–9.
26. Costa P, Sousa Lobo JM. Modelling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123–33.
27. Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose [HPMC]. Adv Drug Delivery Rev 2001;48:139–57.
28. Paroha S, Dubey RD, Mallick S. Physicochemical interaction of naproxen with aluminium hydroxide and its effect on dissolution. Farmacia 2013;61:103–15.
29. Joshi SC. Sol-gel behavior of hydroxypropyl methylcellulose [HPMC] in ionic media including drug release. Materials [Basel] 2011;4:1861–905.
30. Holly FJ, Esquivel ED. Colloid osmotic pressure of artificial tears. J Ocul Pharmacol Ther 2009;1:327–36.
31. Pflugfelder SC, Geerling G, Kinoshita S, Lemp MA, McCulley J, Nelson D, et al. the International dry eye of the workshop [DEWS] 2007 report. Ocul Surf 2007;5:163–78.
32. Lin H, Yiu SC. Dry eye disease: a review of diagnostic approaches and treatments. Saudi J Ophthalmol 2014;28:173–81.
33. Uddin S, Mamun A, Kabir T, Setu JR, Zaman S, Begum Y, et al. Quality control tests for ophthalmic pharmaceuticals: pharmacopeial standards and specifications. J Adv Med Pharm Sci 2017;14:1–17.
34. Bentivoglio AR, Bressman SB, Cassetta E, Carretta D, Tonali P, Albanese A. Analysis of blink rate patterns in normal subjects. Mov Disord 1997;12:1028–34.
35. Sabri LA, Sulaiman HT, Khalil YI. An investigation release and rheological properties of miconazole nitrate from Emulgel. Iraqi J Pharm Sci 2009;18:26–31.
36. Patil S, Kadam A, Bandgar S, Patil S. Formulation and evaluation of an in situ gel for ocular drug delivery of an anticonjunctival drug. Celluler Chem Technol 2015;49:35–40.
37. Mady O. Mechanisms and percent of drug release of each new mathematic approach. Int Res J Pharm Appl Sci 2013;3:56–69.
38. Shaikh HK, Kshirsagar RV, Patil SG. Mathematical models for drug release characterization: a review. World J Pharm Pharm Sci 2015;4:324–38.
39. Aldrich DS, Bach CM, Brown W, Chambers W, Fleitman J, Hunt D, et al. Ophthalmic preparations. In: USP. USP 36–NF 31. Rockville, MD: USP; 2013.
40. Ilic-Stojanovic SS, Nikolic VD, Nikolic LB, Zdravkovic AS. The improved photostability of naproxen in the inclusion complex with 2-hydroxypropyl-?-cyclodextrin. Hem Ind 2015;69:361–70.
41. Vodithala S, Khatry S, Shastri N, Sadanandam M. Development and evaluation of thermosensitive ocular gels of ketorolac tromethamine. Int J Biopharm 2010;1:39–45.
This work is licensed under a Creative Commons Attribution 4.0 International License.