Prednisolone and moxifloxacin compositions and methods
Inventors
Shah, Mandar V. • Subramanian, Ilango • Subramanian, Veerappan • Trehan, Aman
Assignees
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Publication Number
US-12016855-B2
Publication Date
2024-06-25
Expiration Date
Abstract
Provided here are new ophthalmologically suitable pharmaceutical compositions comprising an effective amount of a moxifloxacin compound and an effective amount of a prednisolone compound. In aspects, the compositions are stable suspensions, which maintain physical stability and chemical stability for extended periods of time (e.g., exhibiting no sustained flocculation, coagulation, or clumping after several months of storage under typical storage conditions). In aspects, the compositions are suspensions that include a suspension component comprising one or more suspension agents. In aspects, the suspension component includes an ionic suspension agent. In aspects, the composition also or alternatively comprises a non-ionic surfactant, non-ionic suspension agent, or both, or an agent that provides both functions. In aspects, such compositions further comprise an effective amount of a chelating agent/component. Further described are related compositions and methods of making and using such compositions, e.g., in the treatment of eye infections.
Core Innovation
The disclosed subject matter describes ophthalmologically suitable pharmaceutical suspension compositions that include an ionic suspension component comprising at least one ionic suspension agent and a non-ionic suspension component comprising at least one non-ionic suspension agent, wherein the at least one non-ionic suspension agent does not comprise hydroxypropylmethylcellulose. The suspension comprises at least two pharmaceutical ingredients including moxifloxacin or a pharmaceutically acceptable salt thereof and prednisolone or a pharmaceutically acceptable salt thereof in defined weight-percent ranges, together with a pharmaceutically acceptable chelating agent.
The invention relates to stable ophthalmic suspensions that can be stored and administered without undesirable physical or chemical changes, and addresses chemical degradation and impurity formation in the presence of heat, light/UV, moisture, and pH changes, including oxidation-related impurity behavior. The weight ratio of moxifloxacin or salt to the combination of the ionic and non-ionic suspension components is specified, and certain suspension-component choices can avoid instability such as flocculation, coagulation, and clumping.
The composition is associated with performance characterization of polyoxyl hydrogenated castor oil (Cremophor RH40; also referenced to Cremophor RH-40/Kolliphor RH40 and compared to Cremophor EL), including functional properties relevant to ophthalmic suspensions such as CMC, droplet size, packing parameter, PDI, HLB, and molecular-weight thresholds. These described properties are linked to improved solubility, permeability/bioavailability, reduced impurities, and emulsion droplet size differences versus Cremophor EL, while supporting suspension particle size/stability and content uniformity/potency retention requirements.
Claims Coverage
The independent claim defines an ophthalmologically suitable pharmaceutical suspension with ionic and non-ionic suspension components, specific weight ranges for moxifloxacin and prednisolone, and a pharmaceutically acceptable chelating agent with a defined weight ratio to the suspension components. Two inventive features are consistently present across the supplied claim summaries.
Ionic and non-ionic suspension components
An ophthalmologically suitable suspension includes an ionic suspension component comprising at least one ionic suspension agent, and a non-ionic suspension component comprising at least one non-ionic suspension agent wherein the at least one non-ionic suspension agent does not comprise hydroxypropylmethylcellulose.
Dual active pharmaceutical ingredients in defined ranges
The suspension includes at least two pharmaceutical ingredients comprising moxifloxacin or a pharmaceutically acceptable salt thereof in about 0.01% to about 0.5% by weight of the composition, and prednisolone or a pharmaceutically acceptable salt thereof in about 0.1% to about 5% by weight of the composition.
Chelating agent with defined weight ratio
The suspension includes a pharmaceutically acceptable chelating agent, wherein the weight ratio of moxifloxacin or pharmaceutically acceptable salt thereof to the combination of the ionic suspension component and the non-ionic suspension component is about 1:10 to about 1:32.
Overall, the claim coverage defines a specific ophthalmic suspension formulation architecture combining ionic and non-ionic suspension components with hydroxypropylmethylcellulose excluded, moxifloxacin and prednisolone in defined weight-percent ranges, and a pharmaceutically acceptable chelating agent with a specified weight ratio to the suspension components.
Stated Advantages
Improved solubility.
Improved permeability/bioavailability.
Reduced impurities.
Emulsion droplet size differences versus Cremophor EL.
Suspension performance intended to support suspension stability and content uniformity/potency retention.
Maintains at least about 98% active content over storage conditions.
Maintains total impurities below about 0.5%.
Supports potency retention of at least about 85 w/w.% and up to about 100 w/w.% over months.
Meets composition uniformity and USP acceptability criteria, including a content uniformity equation.
Improved physical/chemical stability over storage, including reduced flocculation, coagulation, and clumping.
Documented Applications
A method of treating or preventing ocular bacterial infection by delivering the composition.
Topical eye administration in a suspension packaged in a drop-delivery device for delivering it to the eye.
Treating or preventing ocular bacterial infection and related inflammation, including topical ophthalmic administration for ocular bacterial or microbial infections with associated inflammation.
Administration in invasive ophthalmic procedure contexts, including cataract surgery and intraocular lens replacement.
Intracameral injection versus topical eye drops.
Ocular bacterial infection indications associated with Streptococcus pneumoniae and Haemophilus influenzae.
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