Nasal formulations of metoclopramide
Inventors
D'Onofrio, Matthew J. • Gonyer, David A. • Shah, Shirish A. • Madden, Stuart J.
Assignees
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Publication Number
US-12194009-B2
Publication Date
2025-01-14
Expiration Date
Abstract
Nasal formulations of metoclopramide, which remain stable and/or colorless upon storage over a period of time, are provided. Also provided are methods of treating disorders treatable with metoclopramide, comprising administering the nasal solutions to patients in need thereof.
Core Innovation
The invention provides metoclopramide nasal formulations that remain stable and substantially colorless/clear during storage. It addresses discoloration observed in prior metoclopramide nasal formulations, including under accelerated storage conditions, and emphasizes citrate buffer with a citrate concentration of at least about 10 millimolar and a composition pH above about 4.5.
The metoclopramide compositions are described with formulation features intended to support stability and color stability, including benzalkonium chloride and optional limits involving benzyl alcohol. The disclosure includes stability and color assessment concepts using visual standards and optical density at 450 nm using iodine standards, and references packaging and storage considerations, including light exposure and oxygen exclusion, as factors related to maintenance of color stability.
The document further describes methods and use in treating metoclopramide-treatable disorders, including gastroparesis and disorders associated with emesis such as emesis, delayed emesis, and nausea. In the provided context, clinical study information for diabetic gastroparesis is referenced, along with dosing regimens using metoclopramide nasal sprays delivered by pump devices.
Claims Coverage
The provided independent claim covers a method of treating gastroparesis via intranasal administration of a metoclopramide composition delivering about 15 mg metoclopramide, or a pharmaceutically-acceptable salt, where the composition includes acetate or citrate at a concentration of at least about 10 millimolar and is effective to treat gastroparesis. The dependent claim refinements further specify intranasal spray form and dosing frequency, and add measurable formulation parameters including benzalkonium chloride concentration and composition pH, plus buffer selection such as sodium citrate.
Intranasal gastroparesis treatment with metoclopramide acetate or citrate buffer
A method of treating gastroparesis by intranasally administering an amount of a metoclopramide composition effective to deliver about 15 mg of metoclopramide, or a pharmaceutically-acceptable salt, wherein the metoclopramide composition comprises acetate or citrate in a concentration of at least about 10 millimolar and wherein the intranasally administering is effective to treat gastroparesis.
Intranasal spray administration form
The method is characterized by intranasal administration using an intranasal spray.
Intranasal spray dosing frequency for gastroparesis treatment
The method is characterized by administering an intranasal spray as one, two, three, or four intranasal sprays per day.
Benzalkonium chloride concentration in the metoclopramide composition
The metoclopramide composition contains benzalkonium chloride at a concentration of about 0.005% (w/v) to about 0.05% (w/v).
Composition pH above 4.5
The method includes using a metoclopramide composition having a pH above about 4.5.
Sodium citrate buffer selection
The buffer includes sodium citrate.
Across the claim set provided, the core inventive coverage is intranasal treatment of gastroparesis using a metoclopramide composition delivering about 15 mg, with acetate or citrate buffer at at least about 10 millimolar, effective for treatment. The dependent refinements further narrow administration to an intranasal spray with specified numbers per day, while adding measurable formulation constraints including benzalkonium chloride concentration, a pH above about 4.5, and buffer selection that includes sodium citrate.
Stated Advantages
Provides metoclopramide nasal formulations that remain stable and substantially colorless/clear during storage.
Addresses discoloration of prior metoclopramide nasal formulations under accelerated conditions.
Documented Applications
Treatment of gastroparesis in a patient using intranasal administration of a metoclopramide composition.
Referenced clinical study context for diabetic gastroparesis with metoclopramide nasal spray dosing regimens.
Treatment of disorders associated with emesis including emesis, delayed emesis, and nausea, as metoclopramide-treatable disorders.
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