Amlodipine formulations
Inventors
BRAUER, Scott • Mosher, Gerold L.
Assignees
Silvergate Pharmaceuticals Inc • Azurity Pharmaceuticals Inc
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12721843-B2
Publication Date
2026-09-01
Expiration Date
Abstract
Provided herein are stable amlodipine oral liquid formulations. Also provided herein are methods of using amlodipine oral liquid formulations for the treatment of certain diseases including hypertension and Coronary Artery Disease (CAD).
Core Innovation
The invention relates to stable oral liquid formulations containing amlodipine benzoate in an amount corresponding to 1.0 mg/ml amlodipine freebase, together with sodium benzoate, a suspension aid, and a non-ionic surfactant, with water as the remaining component. The suspension aid comprises one or more of silicon dioxide, hydroxypropyl methylcellulose, methylcellulose, microcrystalline cellulose, carboxymethyl cellulose sodium, polyvinylpyrrolidone, xanthan gum, or any combination thereof, and the formulation optionally includes a buffer, a flavoring agent, a sweetener, and a preservative.
A key aspect of the formulation is stability under refrigerated storage. The oral liquid formulation is stable at 5±5° C for a storage period of at least 12 months, while maintaining 95% w/w or greater of the initial amlodipine amount and 5% w/w or less total impurities or related substances at the end of the storage period.
The invention addresses formulation stability challenges for amlodipine in oral liquid dosage forms by specifying ingredient categories and performance targets in combination. The formulation employs sodium benzoate at a defined level, and a suspension aid selected from silicon dioxide and specified suspension aids, to maintain suspension characteristics.
Claims Coverage
The document provides at least one independent claim. The main inventive features focus on a defined stable amlodipine benzoate oral liquid composition with specific ingredient ranges and a defined stability and impurity performance target over at least 12 months at 5±5° C; dependent refinements also specify pH, suspension aid concentration, buffer selection and components, and specific surfactant embodiments.
Stable oral liquid formulation with defined excipient ranges
An oral liquid formulation comprising amlodipine benzoate corresponding to 1.0 mg/ml amlodipine freebase; 0.2 mg/ml to 10 mg/ml sodium benzoate; a suspension aid comprising silicon dioxide, hydroxypropyl methylcellulose, methylcellulose, microcrystalline cellulose, carboxymethyl cellulose sodium, polyvinylpyrrolidone, xanthan gum, or any combination thereof; and a non-ionic surfactant present at about 0.1 mg/ml to about 3.0 mg/ml, optionally with one or more selected from a buffer, a flavoring agent, a sweetener, a preservative, and water.
Long-term stability and controlled impurities at 5±5° C.
The oral liquid formulation is stable at 5±5° C. for a storage period of at least 12 months, wherein the stable oral liquid formulation has 95% w/w or greater of the initial amlodipine amount and 5% w/w or less total impurities or related substances at the end of the storage period.
pH-constrained formulation
The oral liquid formulation where the pH is between 4 and 6.
Suspension aid concentration range
The oral liquid formulation characterized such that the suspension aid is present at 5.0 mg/ml to 15.0 mg/ml.
Selected buffer families
The oral liquid formulation where the buffer is a citrate buffer, a phosphate buffer, an acetate buffer, or a combination of these buffers.
Citrate buffer composition
The oral liquid formulation where the citrate buffer includes citric acid and sodium citrate.
Polysorbate surfactant embodiments
The oral liquid formulation where the polyoxyethylene glycol sorbitan alkyl ester is polysorbate 20 or polysorbate 80.
Across the independent claim and the provided dependent refinements, the core inventive concept is a stable amlodipine oral liquid formulation achieving 5±5° C. stability for at least 12 months while maintaining high retained amlodipine content and limiting total impurities or related substances, with dependent claims further constraining pH, suspension aid concentration, buffer selection and components, and specific non-ionic surfactant embodiments.
Stated Advantages
Stable oral liquid formulation at 5±5° C for at least 12 months.
Retains 95% w/w or greater of the initial amlodipine amount after the storage period.
Has 5% w/w or less total impurities or related substances at the end of the storage period.
Documented Applications
Clinical administration regimens for an amlodipine oral liquid, including chronic continuous versus intermittent administration and allowing a "drug holiday" with temporary dose reduction or suspension.
Combination therapies with other cardiovascular agents are described.
A clinical bioavailability crossover study comparing a 5 mg/mL oral suspension to Norvasc® under fasted conditions is described, including reported relative bioavailability measures.
Treating hypertension, including primary hypertension and secondary hypertension.
Treating coronary artery disease (CAD), including chronic stable angina and vasospastic angina.
Administration to children and elderly.
Interested in licensing this patent?