Formulations of pilocarpine and brimonidine compounds and related methods
Inventors
Shah, Mandar V. • Subramanian, Ilango • Subramanian, Veerappan • Trehan, Aman
Assignees
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Publication Number
US-12156868-B2
Publication Date
2024-12-03
Expiration Date
Abstract
The present invention provides stable, pharmaceutically acceptable and ophthalmologically suitable compositions comprising therapeutically effective amounts of both a pilocarpine compound and a brimonidine compound for treating an ocular condition, the compositions comprising a low amount of sodium chloride present in a limited ratio with the active pharmaceutical ingredient(s). In certain embodiments, provided compositions are free of both a borate buffer and a citrate buffer. Compositions provided by the invention surprisingly demonstrate pharmaceutically acceptable stability characteristics when stored under controlled room temperature conditions for an extended period of time. Further, the invention provides methods of manufacturing such compositions in both liquid (solution) and gel form, and methods of their use in treating ocular conditions, such as presbyopia.
Core Innovation
The invention relates to an ophthalmic fixed dose composition for treating an ocular condition by administration to a mammalian eye, where pilocarpine compounds and brimonidine compounds are the only active pharmaceutical ingredients. The composition comprises a pilocarpine compound in an amount between 1.15% w/v and 2.5% w/v and a brimonidine compound in an amount between 0.05% w/v and 0.18% w/v, together with a viscosity enhancer component comprising one or more viscosity enhancing agents.
The composition further includes either a tonicity agent in an amount between 3% w/v and 6% w/v or a quaternary ammonium salt in an amount between 0.003% w/v and about 0.02% w/v. The invention also provides stability requirements expressed as maintaining at least 97% of the pilocarpine compound and at least 97% of the brimonidine compound present upon initial storage under defined temperature and relative humidity storage conditions.
The disclosed approach emphasizes treatment of an ophthalmic condition or symptom related thereto by administering a therapeutically effective amount of an ophthalmologically suitable fixed dose composition. The formulation components are selected to support the stated stability while retaining pilocarpine and brimonidine as the only APIs administered in the method.
Claims Coverage
The independent claims cover two methods of alleviating an ophthalmic condition by administering a fixed-dose ophthalmic composition containing pilocarpine and brimonidine as the only APIs. Four inventive features are identified across the claims, including the fixed-dose ocular administration, the pilocarpine and brimonidine concentration and stability requirements, and the alternative inclusion of either a tonicity agent or a quaternary ammonium salt with a viscosity enhancer component.
Fixed-dose pilocarpine and brimonidine composition for ocular administration
Administration to a mammalian eye of a therapeutically effective amount of a pharmaceutically acceptable and ophthalmologically suitable fixed dose composition, where pilocarpine and brimonidine are the only APIs administered in the method.
Pilocarpine and brimonidine concentration ranges with required stability
A composition comprising a pilocarpine compound in an amount between 1.15% w/v and 2.5% w/v and a brimonidine compound in an amount between 0.05% w/v and 0.18% w/v, maintaining at least 97% of each compound upon initial storage under the stated temperature and relative humidity conditions.
Tonicity agent plus viscosity enhancer component
A composition further comprising a tonicity agent in an amount between 3% w/v and 6% w/v and a viscosity enhancer component comprising one or more viscosity enhancing agents in an amount between 0.1% w/v and 1% w/v.
Quaternary ammonium salt plus viscosity enhancer component
A composition further comprising a quaternary ammonium salt in an amount between 0.003% w/v and about 0.02% w/v and a viscosity enhancer component comprising one or more viscosity enhancing agents in an amount between 0.1% w/v and 1% w/v.
Both independent claims cover methods that administer ophthalmic fixed-dose compositions containing pilocarpine and brimonidine as the only APIs, with defined concentration ranges and at least 97% retention after specified storage conditions. The principal distinction is whether the composition includes a tonicity agent or a quaternary ammonium salt, while both require a viscosity enhancer component.
Stated Advantages
Maintains at least 97% of the pilocarpine compound and at least 97% of the brimonidine compound upon initial storage under the stated temperature and relative humidity storage conditions.
Documented Applications
Alleviating an ophthalmic condition or symptom related thereto by administering a therapeutically effective amount of a fixed dose ophthalmic composition to a mammalian eye.
Treating an ocular condition including presbyopia, hyperopia, mydriasis, anisocoria, accommodative esotropia, myopia, or astigmatism.
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