Effect of percentage of polyvinyl alcohol on the properties of econazole nitrate polymeric micelles eye drop

Ali Hameed; Athmar Dh. H. Al-Shohani; Safar M. Alqahtani

doi:10.32947/ajps.v25i2.1152

Authors

Ali Hameed College of Pharmacy, Mustansiriyah University, Department of Pharmaceutics, Baghdad, Iraq
Athmar Dh. H. Al-Shohani College of Pharmacy, Mustansiriyah University, Department of Pharmaceutics, Baghdad, Iraq
Safar M. Alqahtani College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia

DOI:

https://doi.org/10.32947/ajps.v25i2.1152

Keywords:

Econazole nitrate, Eye drop, Poloxamer 188, Polymeric Micelles, PVA

Abstract

Econazole nitrate, a chemically produced triazole drug, is utilized to manage fungal keratitis. It has potent antifungal properties against many species; the readily available formula exhibits inadequate corneal permeability, visual aberrations, excessive tearing, dilution of tears, and leakage via the nasolacrimal duct.

This research aimed to study the effect of polyvinyl alcohol concentration on the properties of econazole nitrate polymeric micelles eye drops. Polymeric micelles loaded with econazole nitrate eye drops were prepared with different polyvinyl alcohol concentrations and evaluated for particle size, polydispersity index, zeta potential, and drug content. Formulations evaluated for ex vivo drug permeation using Franz diffusion cell. The cumulative drug permeation (CDP) percentage of the optimum formulation exhibits a significant variation of 64.4 % which has 2% of PVA as compared to econazole nitrate pure drug suspension 12.69% CDP. The cumulative drug permeation (CDP) percentage of the optimum formulation F3D demonstrated a 5-fold increase in ex vivo permeability through the goat ocular membrane compared to the econazole nitrate suspension may be attributed to the PVA use as a thickening agent. Using econazole nitrate polymeric micelle as eye drop containing 2% PVA led to system that is efficient and superior in overcoming ocular obstacles and facilitating the appropriate administration of lipophilic medicines by increasing contact time at the ocular surface and improving bioavailability.

References

1- Jumelle C, Gholizadeh S, Annabi N, Dana R. Advances and limitations of drug delivery systems formulated as eye drops. Journal of Controlled Release. 2020 May 10; 321:1-22.

2- Jasib Almzaiel A, Kadhim Hadi Alyasari N. Polymeric micelle improves the bioavailability of low water-soluble phytochemicals. AL-Qadisiyah Journal of Veterinary Medicine Sciences. 2022 Jun 1;21(2):105-14.

3- Li X, Zhang Z, Li J, Sun S, 3-Weng Y, Chen H. Diclofenac/biodegradable polymer micelles for ocular applications. Nanoscale. 2012;4(15):4667-73.

4- Baker, M.I.; Walsh, S.P.; Schwartz, Z.; Boyan, B.D. A review of polyvinyl alcohol

and its uses in cartilage and orthopedic applications. J. Biomed. Mater. Res. B Appl. Biomater. 2012, 100, 1451–1457.

5- Nelson, J.D.; Farris, R.L. Sodium hyaluronate and polyvinyl alcohol artificial tear preparations: A comparison in patients with keratoconjunctivitis sicca. Arch. Ophthalmol. 1988, 106, 484–487.

6- Rowe, R.C.; Sheskey, P.; Quinn, M. Handbook of Pharmaceutical Excipients; Libros Digitales-Pharmaceutical Press: London, UK, 2009.

7- Kokjohn K, Bradley M, Griffiths B, Ghannoum. Evaluation of in vitro activity of ciclopirox olamine, butenafine HCl, and econazole nitrate against dermatophytes, yeasts and bacteria. International Journal of Dermatology. 2003;42(S1):11-7

8- Shah RM, Eldridge DS, Palombo EA, Harding. Microwave-assisted microemulsion technique for production of miconazole nitrate-and econazole nitrate-loaded solid lipid nanoparticles. European Journal of Pharmaceutics and biopharmaceutics. 2017; 117:141-50.

9- 9-Rapoport N. Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Progress in Polymer Science. 2007;32(8):962-990.

10- Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X, et al. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. International Journal of Pharmaceutics. 2009;376(1-2):176-185.

11- Hussein HA, Maraie NK. Highlights on polymeric micelles as versatile nanocarriers for drug transporting. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2021;21(2):21-30.

12- Salman ZD, Maraie NK, Alabbassi MG, Ghareeb MM. In vitro/in vivo evaluation and bioavailability study of amitriptyline hydrochloride from the optimized oral fast dissolving films. Pharmaceutical and Biosciences Journal. 2014 Dec 29:32-42.

13- Epstein SP, Ahdoot M, Marcus E, Asbell PA. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009; 25:113–9.

14- Maraie NK, Almajidi YQ. Application of nanoemulsion technology for preparation and evaluation of intranasal mucoadhesive nano-in-situ gel for ondansetron HCl. Journal of Global Pharma Technology. 2018;10(03):431-2.

15- Kapoor A, Gupta GD. In situ gel for treatment of bacterial conjunctivitis. Int. J. Pharm. Sci. Rev. Res. 2016;40(2):51-7.

16- Li X, Zhang Z, Li J, Sun S, Weng Y, Chen HJN. Diclofenac/biodegradable polymer micelles for ocular applications. 2012;4(15):4667-4673.

17- Shetty GN, Charyulu RN. A study on stability and in vivo drug release of naphazoline and antazoline in situ gelling systems for ocular delivery. Int J Pharm Biol Sci. 2013;4(1):161-71.

18- Kumar D, Jain N, Gulati N, Nagaich U. Nanoparticles laden insitu gelling system for ocular drug targeting. J Adv PharmTechnol Res. 2013;4(1):9-17.

19- Ambalal P, Poddar SS. Scholars Research Library Ophthalmic Minitablet with Natural Polymer: Sterculia Foetida Gum. 2010;2 (1)(0975):467–74.

20- Manjunatha KM, Kulkarni GT, Ismail M. Design and Optimization of Controlled Release Ocular Inserts of Dorzolamide Hydrochloride and Timolol Maleate for Treatment of Glaucoma. Int J Pharm Sci Res. 2012;3(10):3915–22.

21- Lallemand F, Furrer P, Felt-Baeyens O, Gex-Fabry M, Dumont JM, Besseghir K, et al. A novel water-soluble cyclosporine A prodrug: Ocular 97 tolerance and in vivo kinetics. Int J Pharm. 2005;295(1–2):7–

22- Noori MM, Al-Shohani AD, Yousif NZ. Fabrication and characterization of new combination ocular insert for the combined delivery of tinidazole and levofloxacin. Materials Today: Proceedings. 2023 Jan 1;80:2652-9.

23- Thabet Y, Elsabahy M, Eissa NG. Methods for preparation of niosomes: A focus on thin-film hydration method. Methods. 2022;199:9-15.

24- Danaei MR, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018 May 18;10(2):57.

25- Mandal A, Bisht R, Rupenthal ID, Mitra AK. Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies. Journal of Controlled Release. 2017;248:96-116.

26- Gupta A, Costa AP, Xu X, Lee SL, Cruz CN, Bao Q, Burgess DJ. Formulation and characterization of curcumin loaded polymeric micelles produced via continuous processing. International journal of pharmaceutics. 2020 Jun 15;583:119340.

27- Dong Y, Feng SS. Poly (d, l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. Biomaterials. 2005 Oct 1;26(30):6068-76.

28- Suksiriworapong J, Rungvimolsin T, A-gomol A, Junyaprasert VB, Chantasart D. Development and characterization of lyophilized diazepam-loaded polymeric micelles. Aaps PharmScitech. 2014;15:52-64.

29- Saxena V, Hussain MD. Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. Journal of biomedical nanotechnology. 2013;9(7):1146-1154.

30- USP 34-NF 29. BThe United States Pharmacopeia^, 34th, The National formulary 29th: The United States Pharmacopeial Convention, Twinbrook Parkway, Rockville, MD 2011, pp. 700– 1.

31- Nelson, J.D.; Farris, R.L. Sodium hyaluronate and polyvinyl alcohol artificial tear preparations: A comparison in patients with keratoconjunctivitis sicca. Arch. Ophthalmol. 1988, 106, 484–487.

32- Chen YZ, Chen ZY, Tang YJ, Tsai CH, Chuang YL, Hsieh EH, Tucker L, Lin I, Tseng CL. Development of lutein-containing eye drops for the treatment of dry eye syndrome. Pharmaceutics. 2021 Nov;13(11):1801..

33- (Malarvizhi K, Devi DR, Raymond A, Hari BN. Engineered nanoparticle aerosol foam formulation for skin diseases. International Journal of Scientific Engineering and Technology. 2014;3(2):109-15.).

34- Kurniawansyah IS, Rusdiana T, Abnaz ZD, Sopyan I, Subarnas A. Study of isotonicity and ocular irritation of chloramphenicol in situ gel. Int J App Pharm. 2021;13(1):103-7.