Formulation of doxylamine and pyridoxine and/or metabolites or salts thereof
Inventors
VRANDERICK, Manon • ST-ONGE, Jean-Luc • GEDEON, Christelle • GALLO, Michele • Gervais, Éric
Assignees
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Publication Number
US-9937132-B2
Publication Date
2018-04-10
Expiration Date
Abstract
A dual release oral dosage system/dosage form comprising an immediate release component/composition and a delayed release component/composition is described. Each of the immediate release component/composition and delayed release component/composition comprises one or more of doxylamine, an analog thereof, a derivative thereof, a prodrug thereof, a metabolite thereof and/or a salt thereof, and one or more of pyridoxine, a salt thereof, a metabolite thereof and/or a salt of the metabolite. The dual release oral dosage system/dosage form exhibits an improved pharmacokinetic profile relative to the current Diclectin® formulation and is useful for example for the alleviation of the symptoms of nausea and vomiting, for example in the case of nausea and vomiting in pregnancy (NVP).
Core Innovation
The invention relates to a dual release oral dosage system for alleviating the symptoms of nausea and vomiting. The dosage form includes an immediate release composition and a delayed release composition, each comprising doxylamine and pyridoxine components, and the immediate release begins prior to release of the doxylamine and pyridoxine from the delayed release composition within the gastrointestinal tract.
In the disclosed embodiments, the delayed release portion is configured for GI tract release that can be directed to a stomach versus intestine/enteric-like delayed release. The dosage form architecture is described in terms of layered arrangements and core/coats, including delayed-release granules or microspheres combined with immediate-release granules or microspheres.
The document describes pharmacokinetic findings and comparisons, including improved PK behavior versus Diclectin®, with reported changes in concentration-time parameters such as Cmax, AUC, and Tmax. The disclosure includes considerations of food effect and non-linear elimination kinetics, with modeled or simulated regimens intended to support faster or higher plasma levels and reduced timing variability.
Claims Coverage
The partial content provides one independent claim, with multiple dependent claims that refine patient population, administration conditions, dosage-form architecture, and specific pharmaceutically acceptable salt and amount allocations. The core inventive coverage centers on overlapping immediate and delayed release of doxylamine and pyridoxine within the gastrointestinal tract, followed by dependent refinements to structural and dosing specifics.
Overlapping immediate and delayed release of doxylamine and pyridoxine in the gastrointestinal tract
A method for alleviating the symptoms of nausea and vomiting by administering to a human subject a dual release oral dosage form comprising an immediate release composition of doxylamine and pyridoxine and a delayed release composition of doxylamine and pyridoxine, wherein the dosage form comprises from about 10 mg to about 30 mg of doxylamine and from about 10 mg to about 30 mg of pyridoxine, and wherein the immediate release begins prior to release of the doxylamine and pyridoxine from the delayed release composition within the gastrointestinal tract.
Nausea and vomiting of pregnancy in a pregnant woman
The method wherein the human subject is a pregnant woman and the nausea and vomiting is nausea and vomiting of pregnancy (NVP).
Core with delayed-release coating plus additional immediate-release coats
The method wherein the delayed release composition comprises a delayed release core and a delayed release coating, and the method further comprises one or more additional coats comprising an immediate release composition.
Enteric delayed-release coating and constrained doxylamine/pyridoxine salt amounts
The method wherein the core contains about 5 mg to about 15 mg each of doxylamine succinate and pyridoxine hydrochloride, the delayed release coating is an enteric coating, and the one or more coats also comprise about 5 mg to about 15 mg each of doxylamine succinate and pyridoxine hydrochloride.
Specific allocation across core and two identified coats
The method wherein the core contains about 10 mg each of doxylamine succinate and pyridoxine hydrochloride, and the one or more coats include a first coat with about 10 mg pyridoxine hydrochloride and a second coat with about 10 mg doxylamine succinate.
Administration under fasted conditions
The method wherein the dosage form is administered under fasted conditions.
Across the independent claim and refinements provided in the partial content, the claims focus on a dual release oral dosage form in which immediate release of doxylamine and pyridoxine begins before their delayed release within the gastrointestinal tract, with dependent claims narrowing to nausea and vomiting of pregnancy, structural arrangements such as delayed-release core/coating with additional immediate-release coats, specific doxylamine/pyridoxine salt and amount allocations, and administration under fasted conditions.
Stated Advantages
Improved pharmacokinetic behavior versus Diclectin®.
PK findings and modeled or simulated regimens supporting faster or higher plasma levels.
Reduced timing variability.
Documented Applications
Alleviating the symptoms of nausea and vomiting, including nausea and vomiting of pregnancy, by administering the disclosed dual release oral dosage form to a human subject.
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