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-9089489-B2
Publication Date
2015-07-28
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 provides a dual release oral dosage form for effecting relief of nausea and vomiting, comprising an immediate release composition and a delayed release composition. The immediate release composition includes doxylamine and pyridoxine, and the delayed release composition includes doxylamine and pyridoxine, each with pharmaceutically acceptable salt forms.
The dual release dosage form is arranged so that the immediate release and the delayed release components are separated or structurally constrained to control timing and location of release in the gastrointestinal tract. Immediate release occurs in the stomach and delayed or enteric release occurs in the intestine with minimal or no stomach release, using enteric material and coated core or layered arrangements to enable staged release and release interval control.
The invention further addresses formulation and pharmacokinetic behavior by targeting an improved pharmacokinetic profile relative to Diclectin for nausea and vomiting in pregnancy. The disclosed work includes non-linear pharmacokinetic analysis, food effect considerations, and study simulations and comparisons of alternative formulations and dosing regimens.
By using dual release timing in the gastrointestinal tract, the disclosure emphasizes pharmacokinetic characteristics such as Cmax ranges, accumulation behavior, and overall exposure, as described by PK metrics such as AUC and T1/2. The dual release approach is linked to alleviating nausea and vomiting in pregnancy and is discussed in connection with hyperemesis gravidarum and related clinical context.
Claims Coverage
Independent claim coverage is centered on a single independent claim: a dual release oral dosage form with matched doxylamine and pyridoxine in immediate and delayed components, where immediate release begins before delayed component release within the gastrointestinal tract. Dependent coverage further specifies formulation architecture, separation and contact constraints, salt forms and amounts, and use for nausea and vomiting in pregnancy.
Dual release oral dosage form with staged gastrointestinal tract release
A dual release oral dosage form comprising an immediate release composition including doxylamine and pyridoxine and a delayed release composition including doxylamine and pyridoxine, wherein the immediate release composition begins prior to release from the delayed release component within the gastrointestinal tract.
The independent claim defines the core inventive concept as staged dual release of doxylamine and pyridoxine in which the immediate release begins before the delayed release within the gastrointestinal tract; dependent claims then refine the formulation architecture, separation or contact constraints, and specific salt-form compositions, and further specify use for nausea and vomiting in pregnancy.
Stated Advantages
An improved pharmacokinetic profile versus Diclectin for alleviating nausea and vomiting in pregnancy.
Addressing nausea and vomiting in pregnancy, including context of hyperemesis gravidarum, via a dual release approach with controlled gastrointestinal release timing.
Documented Applications
Alleviating nausea and vomiting symptoms in pregnancy, including use tied to a pregnant human female in need.
Contextual use for hyperemesis gravidarum is described.
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