Pharmaceutical formulations comprising CCR3 antagonists
Inventors
FETSCHER, Alfred • SCHER, Jochen Matthias
Assignees
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Publication Number
US-11612596-B2
Publication Date
2023-03-28
Expiration Date
Abstract
The present invention relates to pharmaceutical compositions containing one or more compounds of formula 1 wherein R1 is H, C1-6-alkyl, C0-4-alkyl-C3-6-cycloalkyl, C1-6-haloalkyl;R2 is H, C1-6-alkyl;X is an anion selected from the group consisting of chloride or ½ dibenzoyltartrate;j is 1 or 2; and processes for the preparation thereof, and their use to treat diseases connected with the CCR3 receptor.
Core Innovation
The invention relates to CCR3 antagonist pharmaceutical compositions comprising one or more compounds of Formula 1, wherein R1 is H, C1-6-alkyl, C0-4-alkyl-C3-6-cycloalkyl, or C1-6-haloalkyl; R2 is H or C1-6-alkyl; X is chloride; and j is 2. The compositions are formulated to enable administration as orally deliverable solid dosage forms, including tablets and capsules, optionally film-coated.
The invention addresses formulation challenges for CCR3 antagonist drug substances, including issues related to flowability/compressibility and hydrolytic degradation. The document describes stabilizing formulation strategies through selection of formulation components and stabilization-related ingredients, including pH/buffering agents such as L-arginine and meglumine, together with excipient choices intended to improve stability.
The disclosed dosage forms include oral solid compositions prepared with excipient sets comprising a first diluent that is dibasic calcium phosphate anhydrous, a second diluent, a binder, a disintegrant, and a lubricant. The document further describes film-coated tablets with specific film-coat component categories, and reports stabilization outcomes using degradation/stress and storage/open-storage evaluations to demonstrate improved stability for certain formulations and packaging conditions.
The disclosed CCR3 antagonist compositions are described for treating CCR3-associated diseases, with explicit emphasis on inflammatory/eosinophilic/immunoregulatory and infectious disorders, including respiratory inflammatory/allergic conditions. Ocular and other conditions are also described, including AMD (dry and wet), as well as diabetic retinopathy/ME and ROP, as therapeutic indications for the CCR3 antagonists provided as formulated pharmaceutical compositions.
Claims Coverage
The partial claim set provided contains one independent claim covering a method of administering a CCR3 antagonist pharmaceutical composition with a Formula 1 compound and a defined set of formulation components. Dependent claims further refine the composition’s excipient identities and percentage ranges and narrow the administered dosage form to capsule, tablet, or film-coated tablet with defined film-coating characteristics.
Formula 1 CCR3 antagonist composition with defined excipient set
A method comprising administering a pharmaceutical composition comprising, as an active ingredient, one or more compounds of formula 1 wherein R1 is H, C1-6-alkyl, C0-4-alkyl-C3-6-cycloalkyl, or C1-6-haloalkyl; R2 is H or C1-6-alkyl; X is chloride; and j is 2, together with a first diluent that is dibasic calcium phosphate anhydrous, a second diluent, a binder, a disintegrant and a lubricant.
Percent-range formulation components
The method is characterized by a pharmaceutical composition whose components comprise specified percentage ranges of an active ingredient plus dibasic calcium phosphate anhydrous, a second diluent, a binder, a buffering agent, a disintegrant, and a lubricant.
Oral solid dosage form selection
The method includes administering the composition in a dosage form selected from a capsule, a tablet, or a film-coated tablet.
Film-coated tablet with defined film amount
The method is characterized in that the dosage form includes a 2–4% film coating.
Film coat composition materials
The film coating includes Polyvinyl alcohol (PVA) or hydroxypropylmethylcellulose (HPMC) along with polyethylene glycol (PEG), talc, titanium dioxide, and iron oxide.
Overall, the claim coverage centers on administering a CCR3 antagonist formulation comprising a specified Formula 1 compound (with R1/R2/X/j constraints) together with an excipient system defined by a first diluent (dibasic calcium phosphate anhydrous) plus a second diluent, binder, disintegrant, and lubricant, with dependent claims refining buffering agents, percentage ranges, and film-coated oral solid dosage form features.
Stated Advantages
Improved stability of the CCR3 antagonist formulation in certain formulations/packaging, as described by stress/open-storage degradation outcomes.
Documented Applications
Treating CCR3-associated diseases, including inflammatory/eosinophilic/immunoregulatory disorders and infectious disorders, with particular emphasis on inflammatory/allergic respiratory disorders such as asthma and allergic rhinitis/conjunctivitis.
Treating ocular conditions including AMD (dry and wet).
Treating diabetic retinopathy/ME and ROP.
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