5-hydroxytryptophan gastroretentive dosage forms
Inventors
Jacobsen, Jacob Pade Ramsoe • Berner, Bret • Lin, Wu • Tay, Ching Sieu
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11752107-B2
Publication Date
2023-09-12
Expiration Date
Abstract
A gastroretentive, sustained-release dosage form including 5-hydroxytryptophan (5-HTP) as an active ingredient and low-dose carbidopa is described. For example, the dosage form can be provided as a bilayer tablet comprising a swelling layer and a modified release layer, where the 5-HTP and carbidopa are both included in the modified release layer. The dosage form provides for essentially parallel release of the 5-HTP and the carbidopa with, for instance, release of 80% of the 5-HTP and carbidopa at about 5 hours to about 12 hours.
Core Innovation
The invention provides a gastroretentive dosage form comprising a bilayer tablet having a swelling layer and a modified release layer. The swelling layer comprises one or more hydrophilic polymers swellable in the presence of gastric fluid, and the modified release layer comprises one or more hydrophilic polymers, 5-hydroxytryptophan (5-HTP), and carbidopa.
The bilayer tablet is configured to provide sustained release of both 5-HTP and carbidopa upon administration to a mammalian subject. Dissolution performance in USP Apparatus III defines release behavior, including T=80%(5-HTP) and a relationship between T=80%(5-HTP) and T=80%(carbidopa), with less than a 2 hour difference.
The dosage form also defines specific amounts of drug within the tablet, including about 250 mg of 5-HTP and about 0.3125 mg to about 25 mg of carbidopa. The described approach uses hydrophilic polymers in each layer to support gastric fluid-responsive swelling and modified release, with dissolution targets and quality controls such as content uniformity, stability testing, pharmacokinetics, and gastric retention behavior.
Claims Coverage
The document includes one independent claim covering a gastroretentive bilayer tablet with layer composition and defined dissolution-release performance for both 5-HTP and carbidopa. Dependent claims refine the independent claim by adding quantitative constraints on dissolution windows, swelling/retention behavior, excipient composition, stability, and pharmacokinetic exposure outcomes.
Gastroretentive bilayer tablet with swelling and modified release layers
A gastroretentive dosage form comprising a bilayer tablet having a swelling layer comprising one or more hydrophilic polymers swellable in the presence of gastric fluid and a modified release layer comprising one or more hydrophilic polymers, 5-hydroxytryptophan (5-HTP), and carbidopa, providing sustained release of both upon administration to a mammalian subject.
USP Apparatus III dissolution release window matching for 5-HTP and carbidopa
In dissolution testing in a USP Apparatus III, T=80%(5-HTP) is about 4 hours to about 13.6 hours and T=80%(5-HTP) and T=80%(carbidopa) differ by less than 2 hours.
Tablet drug amounts for 5-HTP and carbidopa
The tablet comprises about 250 mg of 5-HTP and about 0.3125 mg to about 25 mg of carbidopa.
Additional quantified release window refinement
In dissolution testing in a USP Apparatus III, one or both of T=80%(5-HTP) and T=80%(carbidopa) are about 5 hours to about 12 hours.
Swelling performance threshold
The swelling layer swells to at least about 150% of its dry volume in an aqueous solution.
Modified release layer excipient composition definition
The modified release layer composition is defined by specified weight percentages of 5-HTP, carbidopa, microcrystalline cellulose (MCC), medium/high MW PEO, medium- and high-viscosity HPMC, BHT, colloidal silica, and SSF.
Chemical stability requirement under defined storage conditions
The modified release layer remains chemically stable for at least 70 days when stored at about 15°C to about 25°C protected from light.
Pharmacokinetic exposure outcome versus immediate release native 5-HTP
Once or twice daily administration provides about 1-fold to about 10-fold 5-HTP plasma exposure versus immediate release native 5-HTP (same 5-HTP weight) without carbidopa.
Overall claim coverage centers on a gastroretentive bilayer tablet with a swellable hydrophilic polymer swelling layer and a modified release hydrophilic polymer layer containing 5-HTP and carbidopa, with sustained co-release defined by USP Apparatus III dissolution timing and close T=80 alignment. Dependent claims further constrain release windows, swelling behavior, modified-release excipient composition, chemical stability, and pharmacokinetic exposure relative to immediate release native 5-HTP.
Stated Advantages
Sustained release of both 5-HTP and carbidopa upon administration.
Dissolution performance with T=80%(5-HTP) in about 4 hours to about 13.6 hours and T=80%(5-HTP) and T=80%(carbidopa) differing by less than 2 hours.
A chemically stable modified release layer for at least 70 days when stored at about 15°C to about 25°C protected from light.
About 1-fold to about 10-fold 5-HTP plasma exposure versus immediate release native 5-HTP (same 5-HTP weight) without carbidopa, with once or twice daily administration.
Documented Applications
Adjunctive therapy in the context of serotonin reuptake inhibitor (SSRI) adjunctive therapy.
Use in mammals, including administration to mammalian subjects for sustained release of 5-HTP and carbidopa and evaluation using pharmacokinetics and gastric retention behavior.
Interested in licensing this patent?