Chelated, stable ophthalmological compositions of ketorolac and phenylephrine and applications thereof
Inventors
Shah, Mandar V. • Parthasarathi, Kumaresan • Subramanian, Ilango • Subramanian, Veerappan • Trehan, Aman
Assignees
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Publication Number
US-12029729-B2
Publication Date
2024-07-09
Expiration Date
Abstract
This invention provides novel compositions comprising an anti-inflammatory agent and a mydriatic agent suitable for intraocular use, particularly ketorolac or pharmaceutically salts thereof and phenylephrine or pharmaceutically salts thereof, which are free of any buffering agent and yet, surprisingly, maintain stability for significant periods of time (e.g., at least about 3 months). The present invention also relates to a process of preparing such compositions and use thereof, e.g., in combination with intraocular ophthalmologic irrigation solutions.
Core Innovation
The invention relates to a non-lyophilized pharmaceutically acceptable and ophthalmologically suitable liquid composition for use in treating ophthalmic conditions, diseases, or for use in related procedures. The composition comprises pharmaceutically acceptable amounts of a pharmaceutically acceptable salt of ketorolac and a pharmaceutically acceptable salt of phenylephrine, at least one chelating agent, and a carrier.
A key feature is that the composition lacks a buffer component characterized by a combination of a weak base and its conjugate acid, a weak acid and its conjugate base, or both, with the acid and base pairs present in a ratio of ≤1:10. The formulation is buffer-free in the sense of not including such a buffer system meeting the stated ratio and pKa constraints.
The composition is required to retain at least about 97% of the pharmaceutically acceptable salt of ketorolac and at least about 97% of the pharmaceutically acceptable salt of phenylephrine when maintained under storage conditions comprising storage at about 25°C ±2°C for a storage period of at least about three months. The disclosure also describes maintaining stability and limiting impurities during storage.
Claims Coverage
One independent claim is explicitly provided. Its coverage is based on a non-lyophilized ophthalmic liquid composition containing ketorolac and phenylephrine salts plus a chelating agent and a carrier, with a specified absence of a defined buffer component and with retention requirements for both drugs after storage at about 25°C ±2°C for at least about three months.
Buffer-free ketorolac/phenylephrine ophthalmic liquid with defined buffer absence
A non-lyophilized pharmaceutically acceptable and ophthalmologically suitable liquid composition comprising pharmaceutically acceptable amounts of a pharmaceutically acceptable salt of ketorolac and a pharmaceutically acceptable salt of phenylephrine, at least one chelating agent, and a carrier, wherein the composition lacks a buffer component characterized by a combination of a weak base and its conjugate acid, a weak acid and its conjugate base, or both, and the acid and base pairs of the buffer component are present in a ratio of ≤1:10.
High ketorolac and phenylephrine retention during storage
The composition retains at least about 97% of the pharmaceutically acceptable salt of ketorolac and at least about 97% of the pharmaceutically acceptable salt of phenylephrine when maintained under storage conditions comprising storage at about 25°C ±2°C for a storage period of at least about three months.
The claim coverage centers on a buffer-absent non-lyophilized ophthalmic liquid containing ketorolac and phenylephrine salts with a chelating agent and carrier, together with a specified minimum retention of both drug salts after at least three months at about 25°C ±2°C.
Stated Advantages
Maintains high remaining API retention, with at least about 97% retention of the pharmaceutically acceptable salt of ketorolac and at least about 97% retention of the pharmaceutically acceptable salt of phenylephrine after storage for at least about three months at about 25°C ±2°C.
Limits impurities during storage, with described stability data indicating low impurities over up to at least about eight months under accelerated conditions.
Provides buffer-free pH stability as defined by preventing a pH change greater than 2% in the specified pH-change test.
Documented Applications
Use in treating ophthalmic conditions, diseases, or for use in related procedures.
A combined composition for direct topical administration to an eye by mixing the composition with an ocular irrigation solution wherein the irrigation solution constitutes more than about 99% of the total volume.
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