(M1530-07-39) Formulation and Characterization of Gatifloxacin Sesquihydrate Nanostructured Lipid Carriers for Bacterial Conjunctivitis

Purpose: Precorneal retention, drainage, and low bioavailability are all drawbacks associated with the current commercial gatifloxacin (GTX) solution eyedrops. The present study was aimed at preparing and optimizing GTX-loaded nano-lipid carriers (GTX-NLCs) and investigating their potential in ocular applications that might improve ocular retention and bioavailability and reduce the frequency of administration.

Methods: The visual solubility of GTX was screened in different liquid and solid lipids at 80°C. Then the lead liquid and solid lipids underwent saturation solubility studies. The NLCs consisted of GTX (0.5% w/v), oleic acid (liquid lipid) and Precirol^® ATO 5 (solid lipid), glycerin (tonicity adjustment; 2.25% w/v), Tween^® 80 (surfactant), and Milli-Q water (dispersion medium). The NLCs were prepared by hot homogenization followed by probe-sonication. The NLCs were evaluated for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), pH, viscosity, assay, entrapment efficiency (EE), antimicrobial efficacy, and in vitro release. In addition, the lead formulation was subjected to a three-month stability study under refrigerated (4 ± 2°C), room (25 ± 2°C), and accelerated (40 ± 2°C) conditions.

Results: Oleic acid and Precirol^® ATO 5 were selected as the lead lipids after visual solubility studies. The saturation solubility studies showed a saturation solubility of 155 mg of GTX in 1 mL of oleic acid and 80 mg of GTX in 1 gram of Precirol^® ATO 5. NLC placebos were prepared and evaluated to determine any visual incompatibilities. When placebos were prepared with more Precirol^® ATO 5 than oleic acid, a thicker formulation was observed in comparison to a formulation prepared with equal amounts. Three days after preparing drug-loaded formulations prepared with 2% Tween^® 80, the drug was seen to be settling on the bottom of the scintillation vial. This led to the lead formulation of 3% Tween^® 80 and 2.5% of oleic acid and 2.5% of Precirol^® ATO 5. The average PS, PDI, ZP, pH, assay, and EE for the lead formulation were 216 ± 6.8 nm, 0.32 ± 0.03, -27.6 ± 1.2 mV, 6.37, 98.2%, and 90%, respectively on day 0. The in vitro release study showed an extended-release profile over 24 h in phosphate-buffered saline (pH 7.4, 5.0% w/v hydroxypropyl beta-cyclodextrin) (Figure 1). The MIC 90 value (6.25 µg/mL) obtained for the lead NLCs formulation was the same as that of the tested commercial eyedrops against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, GTX-NLCs were stable over two months at all tested storage conditions with respect to PDI, ZP, pH, assay, and EE.

Conclusion: GTX-NLCs were successfully prepared and characterized. However, sterilization and in vivo ocular biodistribution in an animal model are additional studies that are required for the formulation to be developed into an ocular dosage form for topical ocular application.

Figure 1. In vitro release from GTX NLC.