Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas

Abstract

The purpose of this investigation was to evaluate the effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drop through freshly excised goat, sheep, and buffalo corneas. Aqueous isotonic ophthalmic solutions of moxifloxacin hydrochloride of different concentrations (pH 7.2) or 0.5% (wt/vol) solutions of different pH or 0.5% solutions (pH 7.2) containing different preservatives were made. Permeation characteristics of drug were evaluated by putting 1 mL formulation on freshly excised cornea (0.50 cm 2 ) fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated in the receptor (containing 10 mL bicarbonate ringer at 37°C under stirring) by spectrophotometry at 291 nm, after 120 minutes. Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett's test. Increase in drug concentration in the formulation resulted in an increase in the quantity permeated but a decrease in percentage permeation. Increase in pH of the solution from 5.5 to 7.2 increased drug permeation, indicating pH-dependent transport. Compared with control formulation, moxifloxacin 0.5% (wt/vol) solution (pH 7.2) containing disodium edetate (EDTA) (0.01% wt/vol) produced significantly (P G .05) higher permeation with all the corneas. Formulation with benzyl alcohol significantly (P G .05) increased permeation with buffalo cornea compared with its control. Presence of benzalkonium chloride (BAK) (0.01% wt/vol) and EDTA (0.01% wt/vol) in the formulation increased permeation to the maximum with all the corneas. The results suggest that moxifloxacin 0.5% ophthalmic solution (pH 7.2) containing BAK (0.01%) and EDTA (0.01%) provides increased in vitro ocular availability through goat, sheep, and buffalo corneas.

Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops

“…Similar findings of reduced in vitro ocular availability with an increase in drug concentration have been reported for ibuprofen, flurbiprofen, 20,21 and moxifloxacin. 22 An increase in drug concentration did not affect the corneal hydration, however; it remained in the normal range of 75% to 80%. 23 An increase in moxifloxacin hydrochloride concentration from 0.1% to 0.3% (wt/vol) has been found to increase the amount permeated through excised goat cornea by 40% after 120 minutes, 22 whereas gatifloxacin showed a more than 100% increase in permeation under the identical conditions.…”

“…22 An increase in drug concentration did not affect the corneal hydration, however; it remained in the normal range of 75% to 80%. 23 An increase in moxifloxacin hydrochloride concentration from 0.1% to 0.3% (wt/vol) has been found to increase the amount permeated through excised goat cornea by 40% after 120 minutes, 22 whereas gatifloxacin showed a more than 100% increase in permeation under the identical conditions. An increase in the pH of the ophthalmic solution from pH 5 to pH 7.2 increased both the amount of drug permeated and the in vitro ocular availability after 120 minutes (Table 1).…”

“…Corneal hydration remained in the normal range when the pH of the formulation was between 6.5 and 7.2. Transport of moxifloxacin, another fourth-generation fluoroquinolone, across excised goat cornea has also been found to be pH-dependent, with a maximum at pH 7.2, 22 but the pH-induced increase in permeation was much less marked compared with gatifloxacin's.…”

Intraocular pressure and tear secretion in Saanen goats with different ages

“…It is important to study ophthalmopathies in food-producing animals as they play a significant role for economic losses; in addition to improvements made in ophthalmic research, where eyes of goats are commonly used with investigative purposes (Kohli & Rai 1997, Sudan et al 2002, Gilliland et al 2005, Pawar & Majumdar 2007.…”

Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

“…28,29 These values for the tested L-carnosine phytosomes were approximately equal to that of the average surface tension of the tear fluid (43.6±2.7 mN/m) of human eyes. 30 This is likely to allow the carriers to mix uniformly with greater miscibility and minimal disturbance to the precorneal tear film, compared with the drug solution in PBS which has a relatively higher surface tension (76 mN/m).…”