Immediate release dosage forms of sodium oxybate
Inventors
Rourke, Andrea • Allphin, Clark • Murphy, Maura
Assignees
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Publication Number
US-8771735-B2
Publication Date
2014-07-08
Expiration Date
Abstract
The present invention provides a pharmaceutical composition, presented as a solid unit dosage form adapted for oral administration of sodium oxybate. The preferred unit dosage form is a tablet comprising a relatively high weight-percentage of sodium oxybate, in combination with a relatively small weight-percentage of total excipients. This permits the tablets to contain/deliver a pharmaceutically effective amount, e.g., about 0.5-1.5 g of sodium oxybate in each tablet with a delivery profile similar to that of the liquid form. The tablets are bioequivalent to the liquid form.
Core Innovation
The disclosed invention relates to immediate-release oral compressed tablets of sodium oxybate formulated with high sodium oxybate loading and low excipient levels. The tablets are designed to provide dissolution within about one hour when exposed to an aqueous medium and to be bioequivalent, based on AUC/Cmax, to sodium oxybate oral solution (Xyrem®).
The invention addresses tablet composition by specifying sodium oxybate content of 80-95 wt %, together with compression aid and binder components within defined ranges. The document further describes excipient concepts including microcrystalline cellulose and binder materials, and it discusses optional use or exclusion of super-disintegrants as part of the formulation approach. Surfactants are also described in the context of supporting immediate release performance, with examples including sodium lauryl sulfate and poloxamer.
The invention also encompasses manufacturing and optional protective features. The document describes a roller compaction approach and includes optional moisture- or water-resistant coating concepts using polyvinyl alcohol (PVA) and lecithin, e.g. Opadry® AMB, to form a protective coating layer. Exemplified tablet formulations and in vivo PK/bioequivalence results are presented relative to Xyrem®, along with dissolution profile demonstrations for immediate release.
Claims Coverage
The independent claims cover three related dosage-form frameworks: a compressed tablet of sodium oxybate that is bioequivalent to sodium oxybate oral solution, an immediate release unit dosage form with defined release performance within one hour, and a compressed tablet of an oxybate salt that is bioequivalent to sodium oxybate oral solution. Across these independent claims, the main inventive features are high oxybate or sodium oxybate loading, constrained excipient ranges, defined immediate-release dissolution or release criteria, and bioequivalence to the sodium oxybate oral solution framework.
Bioequivalent sodium oxybate compressed tablet composition
A compressed tablet of sodium oxybate for oral delivery of 0.5-1.25 g of sodium oxybate comprising 80-95 wt % sodium oxybate; 5-10 wt % compression aid; and 1-50% binder; wherein the tablet is bioequivalent to sodium oxybate oral solution.
Immediate release unit dosage form with one-hour release
An immediate release unit dosage form comprising an about 0.5-1.5 g compressed tablet comprising 80-95 wt-% sodium oxybate; about 2.5-7.5 wt-% microcrystalline cellulose and about 0.25-2.5 wt-% surfactant, wherein at least 90% of the sodium oxybate is released from the tablet within one hour from exposure of the tablet to an aqueous medium.
Bioequivalent oxybate salt compressed tablet composition
A compressed tablet of an oxybate salt for oral delivery of 0.5-1.25 g of oxybate salt comprising 80-95 wt % oxybate salt; 5-10 wt % compression aid; and 1-50% binder; wherein the tablet is bioequivalent to sodium oxybate oral solution.
Overall, the claim set establishes compressed oral dosage forms centered on high sodium oxybate or oxybate-salt loading, specific compression aid and binder ranges, immediate-release performance including at least 90% release within one hour for the immediate-release unit dosage form, and a bioequivalence relationship to sodium oxybate oral solution (Xyrem®).
Stated Advantages
Immediate-release dissolution performance within about one hour in an aqueous medium.
Bioequivalence to sodium oxybate oral solution (AUC/Cmax bioequivalence relative to Xyrem® is described).
Documented Applications
Oral administration to treat narcolepsy or related disorders including excessive daytime sleepiness and cataplexy is described in the document context.
The document also references restless leg syndrome, essential tremor, fibromyalgia, chronic fatigue syndrome as disorders associated with the disclosed oral administration use context.
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