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Glenwood G Gum, Joe Rager, Jessica Helwig, Barbara Wirostko, MaryJane Rafii; Ocular Distribution of Moxifloxacin (MX) from Sustained-Releasing (SR) Hydrogel Films in New Zealand White (NZW) Rabbits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4715.
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Moxifloxacin is a marketed fluoroquinolone ophthalmic solution used to treat bacterial conjunctivitis and corneal ulcers. For ulcers, treatment includes hourly applications for several days. To improve patient compliance, alternate dosing regimens and drug delivery options are being evaluated. Jade developed a SR system, a Hystem Hyaluronic acid (HA) film loaded with MX, applied to the lower fornix of the eye, reducing multiple applications. Absorption Systems developed an LC-MS/MS method to evaluate MX distribution in ocular tissue.
Films were applied to the eyes of NZW rabbits 3 weeks after third eyelid was removed. OD eye were treated with MX film, OS received SR (Hystem film) only or untreated control. Tears and aqueous humor(AH) samples were collected at Day 1, 2, 3, 5, and 7. An n=6 per group/day of which 3 rabbits received a low dose (30 µg/eye) and 3 received a high dose (100 µg/eye). AH was collected via paracentesis; tears were collected via capillary tube placed at medial canthus; conjunctival tissue was collected from enucleated eyes. LC MS/MS method for MX was developed and qualified in simulated tear fluid and NZW AH and conjunctival tissues. Conjunctival samples were homogenized with a polytron in 20% methanol:water. Samples were extracted via acetonitrile precipitation and analyzed against calibration standards.
The method was qualified in each of the matrices to assess accuracy and precision over a range of 0.5 to 1000 ng/mL. All AH samples were below the limit of quantitation, 0.5ng/mL (BLOQ). Conjunctival tissue show MX levels in the high dose group on Day 1; the low dose and high dose groups of the remaining days were BLOQ. Low dose MX in the tear fluid ranged from 2.22 ng/mL on Day 1 to 8.75 ng/mL Day 2, and BLOQ on Day 3-7. The high dose tear levels were from 11.1 ng/mL Day 1 to 1.72 Day 2, Day 3 0.70 ng/mL, and BLOQ from Day 5. No levels of MX were detached in the OS eyes.
MX film retention was best when placed in the lower fornix. High dose MX film showed superior levels over time in tears and conjunctiva, and apparently cornea, vs. low dose MX film. Studies are in development to improve ocular surface retention time in order to extend drug release on the ocular surface. This data is consistent with Jade’s efficacy and in vitro release data.
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