Comparison of Vehicles for Vancomycin Drug Delivery in Extemporaneously Prepared Ophthalmic Solutions

Abstract

This work compares the ophthalmic delivery of vancomycin 50 mg/ml eye drops using 5 different vehicles, namely: 0.3% w/v chitosan, 0.3% and 0.4% w/v HPMC (Methocel E4M), Tears NaturaleTMII and 0.9% w/v sodium chloride solution.In vitroandin vivostudies were carried out and the results evaluated in terms of viscosity, compatibility, stability, clarity, minimum inhibitory concentration (MIC) and pharmacokinetics. The viscosity of Tears NaturaleTMII was comparable with that of HPMC (0.3% pH 7.1) but was higher than 0.3% w/v chitosan. The percent labeled amounts and MIC of vancomycin 50 mg/ml in all of the vehicles were stable for 30 days at 2-8°C, while the clarity in 0.3% w/v chitosan, 0.3% and 0.4% HPMC (pH 7.1), Tears NaturaleTMII and 0.9% sodium chloride solution was stable for 30, 14, 1 and 3 days respectively at 2-8°C.In vivopharmacokinetic determinations of the AUC of tear film reciprocal of minimum inhibitory titer showed that vancomycin 50 mg/ml in 0.3% w/v chitosan, 0.3% and 0.4% w/v HPMC pH 7.1 and Tears NaturaleTMII were significantly different from 0.9% sodium chloride solution. At the present time, chitosan is undergoing clinical trials in Thailand with a view to its use in ophthalmology, while HPMC (0.3% w/v) in pH 7.1 has already been approved for use as a vehicle in ophthalmology for the delivery of vancomycin 50 mg/ml in extemporaneous eye drops.

Use of chitosan as pharmaceutical excipient in ocular drug delivery systems: Sterilization and pharmacokinetics

“…natural nontoxic biopolymer produced by the deacetylation of chitin, a major component of the shells of crustaceans (Georgieva, Zvezdova, & Vlaev, 2012). It is well established that formulations containing CS are able to enhance precorneal residence time and ocular bioavailability of several drugs, such as terbinafine (Tayel, El-Nabarawi, Tadros, & Abd-Elsalam, 2013), gatifloxacin (Abul Kalam et al, 2013), amphotericin B (Song, Zhou, Wang, & Jian, 2013), natamycin (Bhatta et al, 2012), vancomycin (Khangtragool, 2012), dorzolamide (Warsi et al, 2011), mycophenolate mofetil (Wu, Xin, Yang, & Shi, 2011), indomethacin (Yamaguchi et al, 2009), timolol (Cao et al, 2007), ofloxacin (Zambito & Di Colo, 2010), bimatoprost (Franca et al, 2014), and tobramicyn (Felt, Baeyens, Buri, & Gurny, 2001). Moreover, the ability of CS to effectively interact with the ocular mucosa has been attributed not only to its cationic charge but also to its intrinsic properties (de la Fuente et al, 2010).…”