Voriconazole is a novel antifungal agent with excellent broad spectrum activity commercially available for oral and intravenous administration. The purpose of this study was to prepare ophthalmic formulation of hydroxypropyl beta cyclodextrin (HP- -CD) based voriconazole containing benzalkonium chloride BAK and EDTA with or without viscosity modifiers and study its permeation characteristics through freshly excised goat cornea. The results were observed that viscosity and force of bioadhesion of the voriconazole HP- -CD solutions containing xanthan gum (XG) are more as compared to polyvinyl alcohol. The results revealed that voriconazole drop containing PVA provided least viscosity and higher corneal permeation of drug, while drop formulated with XG had maximum viscosity and least permeation. The HP- -CD based voriconazole (1.5%) ophthalmic formulation containing xanthan gum (1.5), preserved with BAK and EDTA, could provide shelf life of 2 years. The microbiological studies showed that voriconazole ophthalmic solution containing xanthan gum shows better antifungal activity as compared to voriconazole and xanthan gum alone. Thus, it can be concluded that HP- -CD based voriconazole (1.5%, pH 7.0) ophthalmic solution containing BAK and EDTA with viscosity modifier XG provided maximum precorneal residence time as compared to other viscosity modifiers and polyvinyl alcohol provided less precorneal residence time than other viscosity modifiers. 1. Introduction The inflammatory disorders of the eye parts are the manifestations of the bacterial, fungal and viral infections. Staphylococcus aureus (due to injury), Pseudomonas aeruginosa (may be due to contact lens), Streptococcus, herpes simplex type I, varicella zoster, Cytomegalovirus (CMV), adenovirus, Candida species, and Actinomyces israelii are the major bacterial, viral, and fungal organisms that infect the different parts of the eyeball causing decreased vision, pain, and red eyes and may even lead to blindness [1]. Fungal keratitis is one of the major causes of ophthalmic mycosis, accounting for more than 50% of proven ophthalmic mycoses in some countries. Fungal keratitis is usually characterized by a corneal epithelial defect and inflammation of the corneal stroma. If untreated, fungal keratitis can lead to corneal scarring and vision loss. Fungal keratitis is most common in tropical regions and developing countries, where it constitutes over 50% of keratitis. The ultimate goal in the treatment of fungal keratitis is to conserve vision. This requires timely diagnosis of the infection and administration
References
[1]
J. D. Henderer and C. J. Raprano, “Ocular pharmacology,” in Goodman & Gilman’s the Pharmacological Basis of Therapeutics, L. L. Brunton, J. S. Lazo, and K. L. Parker, Eds., pp. 1707–1737, McGraw-Hill, New York, NY, USA, 11th edition, 2005.
[2]
B. Manzouri, R. K. H. Wyse, and G. C. Vafidis, “Pharmacotherapy of fungal eye infections,” Expert Opinion on Pharmacotherapy, vol. 2, no. 11, pp. 1849–1857, 2001.
[3]
L. B. Johnson and C. A. Kauffman, “Voriconazole: a new triazole antifungal agent,” Clinical Infectious Diseases, vol. 36, no. 5, pp. 630–637, 2003.
[4]
D. Lau, M. Fedinands, L. Leung et al., “Penetration of voriconazole, 1%, eyedrops into human aqueous humor: a prospective open-label study,” Archives of Ophthalmology, vol. 126, no. 3, pp. 343–346, 2008.
[5]
S. Gupta, R. M. Shrivastava, R. Tandon, V. Gogia, P. Agarwal, and G. Satpathy, “Role of voriconazole in combined acanthamoeba and fungal corneal ulcer,” Contact Lens and Anterior Eye, vol. 34, no. 6, pp. 287–289, 2011.
[6]
R. D. Schoenwald, “Controlled drug bioavailability,” in Bioavailability Control by Drug Delivery System Design, V. F. Smolen and L. Bull, Eds., pp. 257–306, John Wiley & Sons, New York, NY, USA, 1985.
[7]
A. Dupuis, N. Tournier, G. le Moal, and N. Venisse, “Preparation and stability of voriconazole eye drop solution,” Antimicrobial Agents and Chemotherapy, vol. 53, no. 2, pp. 798–799, 2009.
[8]
M. A. Halim Mohamed and A. A. Mahmoud, “Formulation of indomethacin eye drops via complexation with cyclodextrins,” Current Eye Research, vol. 36, no. 3, pp. 208–216, 2011.
[9]
H. Fridriksdóttir, T. Loftsson, and E. Stefánsson, “Formulation and testing of methazolamide cyclodextrin eye drop solutions,” Journal of Controlled Release, vol. 44, no. 1, pp. 95–99, 1997.
[10]
R. Nijhawan and S. P. Agarwal, “Development of an ophthalmic formulation containing ciprofloxacin-hydroxypropyl-b-cyclodextrin complex,” Bollettino Chimico Farmaceutico, vol. 142, no. 5, pp. 214–219, 2003.
[11]
E. E. Hassan and J. M. Gallo, “A simple rheological method for the in vitro assessment of mucin-polymer bioadhesive bond strength,” Pharmaceutical Research, vol. 7, no. 5, pp. 491–495, 1990.
[12]
“Q1A (R2): stability testing of new drug substances and products,” in Proceedings of the International Conference on Harmonization (ICH '03), Geneva, Switzerland, 2003.
[13]
H. W. Oviatt Jr. and D. A. Brant, “Thermal treatment of semi-dilute aqueous xanthan solutions yields weak gels with properties resembling hyaluronic acid,” International Journal of Biological Macromolecules, vol. 15, no. 1, pp. 3–10, 1993.
[14]
L. D. Melton, L. Mindt, and D. A. Rees, “Covalent structure of the extracellular polysaccharide from Xanthomonas campestris: evidence from partial hydrolysis studies,” Carbohydrate Research, vol. 46, no. 2, pp. 245–257, 1976.
[15]
S. K. Paliwal, R. Chauhan, V. Sharma, D. K. Majumdar, and S. Paliwal, “Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery,” Indian Journal of Pharmaceutical Sciences, vol. 71, no. 6, pp. 687–691, 2009.
[16]
G. M. Grass, R. W. Wood, and J. R. Robinson, “Effects of calcium chelating agents on corneal permeability,” Investigative Ophthalmology and Visual Science, vol. 26, no. 1, pp. 110–113, 1985.
[17]
S. Burgalassi, P. Chetoni, D. Monti, and M. F. Saettone, “Cytotoxicity of potential ocular permeation enhancers evaluated on rabbit and human corneal epithelial cell lines,” Toxicology Letters, vol. 122, no. 1, pp. 1–8, 2001.
[18]
N. L. Burstein, “Preservative alteration of corneal permeability in humans and rabbits,” Investigative Ophthalmology and Visual Science, vol. 25, no. 12, pp. 1453–1457, 1984.
[19]
D. L. van Horn, H. F. Edelhauser, and G. Prodanovich, “Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium,” Investigative Ophthalmology & Visual Science, vol. 16, no. 4, pp. 273–280, 1977.
[20]
M. Malhotra and D. K. Majumdar, “Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine,” Indian Journal of Experimental Biology, vol. 40, no. 5, pp. 555–559, 2002.
[21]
D. M. Maurice and M. V. Riley, “Ocular pharmacokinetics,” in Biochemistry of the Eye, pp. 6–16, Graymore, London, UK, 1970.
