once a day oral administration formulation contains trazodone or salt, phosphorus oxychloride cross-linked high amylose starch, hydroxypropylmethylcellulose, sodium stearyl fumarate, colloidal silica, optional cetylpyridinium chloride and alganic acid; antidepressant; sleep disorder; sustained release
Inventors
Gervais, Sonia • Smith, Damon • Rahmouni, Miloud • Contamin, Pauline • Ouzerourou, Rachid • Ma, My Linh • Ferrada, Angela • Soulhi, Fouzia
Assignees
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Publication Number
US-7829120-B2
Publication Date
2010-11-09
Expiration Date
Abstract
The invention relates to a once a day formulation of trazodone or a trazodone derivative. The formulation contains trazodone or a trazodone derivative and a controlled release excipient so that, once administered orally, the trazodone or the trazodone derivative is maintained at a therapeutic plasma concentration from at least 1 hour to at least 24 hours after initial administration. After administration, the initial therapeutic action takes effect within the first hour and lasts at least about 24 hours. This therapeutic effect remains relatively and substantially stable for the remaining period of 24 hours. The formulations can be used for treating depression and/or sleeping disorders.
Core Innovation
The invention relates to a sustained release pharmaceutical composition for once a day oral administration comprising trazodone or a derivative thereof. The formulation is designed to release the trazodone or the derivative thereof after oral administration so as to maintain a substantially constant effective plasma concentration over an extended time period.
A key component of the composition is a cross-linked high amylose starch formed by phosphorus oxychloride cross-linking, including phosphorus oxychloride cross-linked high-amylose starch such as CONTRAMID®. The composition may further include hydroxypropylmethylcellulose as a binder and may optionally include cetylpyridinium chloride and alginic acid.
To support controlled release behavior, the composition can include sodium stearyl fumarate and up to colloidal silicon dioxide as lubricants/glidants. The release is described as pH-independent controlled release to address trazodone pH-dependent solubility, maintaining stable therapeutic plasma concentrations between about 50 ng/mL and about 3000 ng/mL from at least about one hour to at least about 24 hours.
Claims Coverage
The partial content includes one independent claim. This independent claim specifies a sustained release once-daily oral trazodone composition with a defined quantitative excipient composition and a release outcome defined by maintaining a substantially constant effective plasma concentration between about 50 ng/mL and about 3000 ng/mL from at least about one hour to at least about 24 hours, yielding pH-independent controlled release behavior.
Substantially constant plasma concentration over 24 hours
The composition releases the trazodone or the derivative thereof when administered orally to a mammal to maintain a substantially constant effective plasma concentration between about 50 ng/mL and about 3000 ng/mL from at least about one hour to at least about 24 hours after initial administration.
Cross-linked high amylose starch excipient system
The composition comprises about 20% to about 50% by weight of cross-linked high amylose starch as a controlled release excipient.
Defined trazodone and formulation excipient ranges
The composition comprises about 20% to about 50% by weight of trazodone or a derivative thereof, about 10% to about 25% by weight of hydroxypropylmethylcellulose, about 0% to about 5% by weight of cetylpyridinium chloride, about 0% to about 20% by weight of alginic acid, about 1% to about 5% by weight of sodium stearyl fumarate, and up to about 1% by weight of colloidal silicon dioxide.
Across the independent claim, the inventive coverage is centered on a once-daily oral sustained release trazodone composition using a cross-linked high amylose starch excipient system in combination with hydroxypropylmethylcellulose and optional additional excipients, configured to maintain a substantially constant effective plasma concentration between about 50 ng/mL and about 3000 ng/mL from about one hour to at least about 24 hours.
Stated Advantages
Maintains a substantially constant effective plasma concentration between about 50 ng/mL and about 3000 ng/mL from at least about one hour to at least about 24 hours after initial administration.
Provides pH-independent controlled release, addressing trazodone pH-dependent solubility.
Reduces daytime drowsiness or somnolence.
Documented Applications
Treating depression.
Treating sleep disorders.
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