Quinolone dispersions
Inventors
Shah, Mandar V. • Subramanian, Ilango • Subramanian, Veerappan • Trehan, Aman
Assignees
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Publication Number
US-12102632-B2
Publication Date
2024-10-01
Expiration Date
Abstract
Provided are new ophthalmologically suitable pharmaceutical compositions comprising an effective amount of a quinolone antibiotic, e.g., a fourth-generation fluoroquinolone, and an effective amount of an anti-inflammatory agent. In aspects, the anti-inflammatory agent is an anti-inflammatory steroid, NSAID, or a combination thereof. In aspects, compositions are stable suspensions, which maintain physical and chemical stability for extended periods of time (e.g., exhibiting no sustained flocculation, coagulation, or clumping after several months of storage under typical conditions). In aspects, compositions are suspensions including a suspension component comprising one or more suspension agents. In aspects, the suspension component includes an ionic suspension agent. In aspects, compositions also or alternatively comprise a non-ionic surfactant, non-ionic suspension agent, or both, or an agent providing both functions. In aspects, compositions further comprise a chelating agent/component. Further described are related compositions and methods of making and using such compositions, e.g., in treating or preventing of bacterial eye infections.
Core Innovation
The invention relates to an ophthalmologically suitable pharmaceutical composition in the form of a suspension. The composition comprises a suspension agent component and an active pharmaceutical ingredient component, and the active pharmaceutical ingredient component consists of a fluoroquinolone antibiotic component and an anti-inflammatory component.
The suspension agent component comprises at least two suspension agents, including at least one ionic suspension agent and at least one non-ionic suspension agent. The ionic suspension agent is present in an amount of between 0.2% and 2% by weight, the non-ionic suspension agent is present in an amount of between 0.5% and 2% by weight, and the ionic suspension agent has an average molecular weight of at least about 1,000 Da.
The fluoroquinolone antibiotic component comprises at least one fluoroquinolone antibiotic compound present in an amount representing 0.01% to 1% by weight, and the anti-inflammatory component comprises at least one steroid anti-inflammatory compound present in an amount representing 0.1% to 5% by weight. The composition also specifies ratios linking the anti-inflammatory component to the ionic suspension agent and to the combination of the ionic and non-ionic suspension agents, and the steroid anti-inflammatory compound is selected from triamcinolone, prednisolone, and loteprednol, while the fluoroquinolone antibiotic compound is moxifloxacin or gatifloxacin.
Claims Coverage
One independent claim is provided. The claim defines an ophthalmologically suitable suspension composition with a two-part active ingredient system and a two-type suspension-agent system, together with quantitative weight ranges, component ratios, and named compound selections.
Ionic and non-ionic suspension-agent component for an ophthalmic suspension
A suspension agent component comprising at least two suspension agents including at least one ionic suspension agent present in an amount between 0.2% and 2% by weight and at least one non-ionic suspension agent present in an amount between 0.5% and 2% by weight, with an average molecular weight of at least about 1,000 Da for the ionic suspension agent.
Fluoroquinolone antibiotic plus steroid anti-inflammatory active components
An active pharmaceutical ingredient component consisting of a fluoroquinolone antibiotic component and an anti-inflammatory component, where the fluoroquinolone antibiotic component comprises at least one fluoroquinolone antibiotic compound present in an amount representing 0.01% to 1% by weight and the anti-inflammatory component comprises at least one steroid anti-inflammatory compound present in an amount representing 0.1% to 5% by weight.
Anti-inflammatory to suspension-agent ratio constraints
A ratio of the anti-inflammatory component to the at least one ionic suspension agent between 1:20 and 15:1, and a ratio of the anti-inflammatory component to a combination of the at least one ionic suspension agent and the at least one non-ionic suspension agent of 2.5:1 to 1:120.
Specific fluoroquinolone and specific steroid selection
Where the at least one fluoroquinolone antibiotic compound is moxifloxacin or gatifloxacin and the at least one steroid anti-inflammatory compound is triamcinolone, prednisolone, or loteprednol.
The claim is defined by a suspension-agent component containing specified amounts of ionic and non-ionic suspension agents, an active pharmaceutical ingredient component combining a fluoroquinolone antibiotic with a steroid anti-inflammatory, and defined ratio constraints between the anti-inflammatory component and the suspension agents, with named compound selections.
Stated Advantages
Provides a non-irritating profile compared with polyoxyethylene-polyoxypropylene block copolymers.
Allows injectability through 27G needles without clogging after shaking.
Maintains acceptable viscosity.
Maintains pH stability.
Maintains osmolality within specified ranges.
Provides broad physical and chemical stability, including API potency retention and low impurity levels.
Maintains stability against flocculation, clumping, or coagulation over storage conditions.
Improved solubility/permeability/bioavailability.
Increased suspension retention and stability under storage.
Reduced adverse effects, including inert/non-irritating and non-foaming.
No major hypersensitivity/toxicity.
Documented Applications
Treatment and/or prevention of ocular infections and inflammation using the ophthalmic suspension composition, including intracameral injection and topical drops.
Ocular infectious and inflammatory conditions involving bacterial conjunctivitis, including bacteria such as Streptococcus and Haemophilus.
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