title: Mucoadhesive dexamethasone acetate-polymyxin B sulfate cationic ocular nanoemulsion--novel combinatorial formulation concept.
abstract: Dexamethasone acetate (DEX) and polymyxin B sulfate (polymyxin B) were formulated as a cationic nanoemulsion for the treatment of ophthalmic infections. As novel concept, the positive charge to achieve mucoadhesion was not generated by toxicologically and regulatorily problematic cationic lipids or polymers, but by using a positively charged drug in combination with positively charged preservatives. The preservative also acts as co-surfactant to stabilize the emulsion. Nanoemulsions with the lipid phase Eutanol G-Lipoid S 100 (70%:30%) containing 0.05% (w/w) DEX were produced by high pressure homogenization, followed by dissolving the hydrophilic molecules in the water phase, e.g. polymyxin B (0.1%, w/w), cetylpyridinium chloride (0.01%, w/w) and glycerol (2.6%, w/w) to yield a combination product. The particles were below 200 nm with narrow size distribution. The osmolality (374 mOsm/kg), pH (5.31) and viscosity (2.45 mPa s at 37 degrees C) were compatible to the ocular administration. The zeta potential of the optimized formulation was shifted from approx. +9 mV to -11 mV after mucin incubation. The in vitro test revealed no potential cytotoxicity. The final products were stable after 180 days of storage at 4 degrees C and room temperature. The developed product is a viable alternative to the commercial ophthalmic suspensions. Moreover, this concept of generating the positive charge by cationic drug and/or preservative addition can be transferred to other ophthalmic products.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.forename: C M
authors.initials: CM
authors.lastname: Keck
authors.forename: N A
authors.initials: NA
authors.lastname: Bou-Chacra
mesh_terms: D060433:Administration, Ophthalmic; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004338:Drug Combinations; D004355:Drug Stability; D004655:Emulsions; D053758:Nanoparticles; D009883:Ophthalmic Solutions / Q000737:chemistry*; D009994:Osmolar Concentration; D010316:Particle Size; D011112:Polymyxin B / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D004655:Emulsions; D009883:Ophthalmic Solutions; D003907:Dexamethasone; C018038:dexamethasone acetate; D011112:Polymyxin B