Moisture resistant container systems for rapidly bioavailable dosage forms
Inventors
Reiner, Giorgio • Reiner, Alberto
Assignees
ARP APPLIED PHARMA RESARCH SA • Kowa Pharmaceuticals America Inc
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Publication Number
US-7700125-B2
Publication Date
2010-04-20
Expiration Date
Abstract
Provided are rapidly bioavailable solid oral dosage forms of acute pain medications, and moisture resistant packaging that enables the formulation of such rapidly bioavailable dosage forms.
Core Innovation
The patent relates to rapidly bioavailable solid oral dosage forms of diclofenac potassium for acute pain medications and addresses the problem that such dosage forms soften when exposed to moisture. Moisture uptake reduces rapid-bioavailability performance by affecting tablet integrity and the ability to disintegrate and/or dissolve rapidly.
The core discovery is that counteracting moisture uptake through a specifically defined diclofenac potassium tablet formulation and moisture resistant bottle packaging preserves rapid bioavailability. The formulation includes at least 20 wt. % of one or more alkali metal carbonate or bicarbonate salt excipients that are freely soluble in water, together with a hygroscopic diluent and said freely soluble diluent at a specified weight ratio, with hygroscopic diluent water uptake behavior defined in a humidity chamber at 60% RH and 25 °C.
The patent further links the formulation to packaging performance by requiring storage in a moisture resistant bottle that prevents the dosage form from absorbing more than a defined amount of moisture over three months at 40 °C and 75% relative humidity. The disclosed approach specifies rapid-bioavailability outcomes using pharmacokinetic and disintegration/dissolution criteria and describes moisture-resistant packaging elements including hermetic/foil sealing and optional desiccant pouches.
Claims Coverage
The independent claim is directed to packaging a defined 50 mg diclofenac potassium rapid-bioavailability tablet formulation with a moisture resistant bottle having a defined moisture-uptake limit. The inventive features across the claims include quantitative pharmacokinetic performance criteria, a single Cmax peak, and further refinement of excipients and packaging components.
Packaging a rapidly bioavailable 50 mg diclofenac potassium tablet
A method of packaging a rapidly bioavailable diclofenac potassium tablet, wherein the dosage form is a 50 mg diclofenac potassium tablet dosage form for rapid bioavailability.
At least 20 wt% water-soluble alkali metal carbonate or bicarbonate excipients
A formulation comprising at least 20 wt. % of one or more alkali metal carbonate or bicarbonate salt excipients that are freely soluble in water.
Defined hygroscopic diluent and freely soluble diluent weight ratio with water uptake behavior
From about 30 to about 80 wt % of a hygroscopic diluent and said one or more freely soluble diluents at a weight ratio of from about 1:20 to about 5:1, wherein said hygroscopic diluent absorbs greater than about 0.5 wt. % water within a twenty four hour period in a humidity chamber maintained at 60% relative humidity and 25 °C.
Moisture resistant bottle with moisture-uptake limit under accelerated storage
Packaging said dosage form in a moisture resistant bottle that prevents said dosage form from absorbing more than 4 wt. % moisture in three months when stored at 40 °C and 75% relative humidity.
Rapid bioavailability with defined tmax and Cmax ranges
The method is characterized by rapid bioavailability characterized by a tmax of about 5 to about 30 minutes and a Cmax of about 1700 to about 2300 ng/ml.
Rapid bioavailability with defined tmax, Cmax, and inter-subject variability
The method is characterized such that rapid bioavailability is characterized by specified time to maximum plasma concentration, maximum plasma concentration, and inter-subject variability limits.
Single maximum plasma concentration (Cmax) peak
The dosage form produces a single maximum plasma concentration (Cmax) peak after ingestion.
Sodium lauryl sulfate included in the dosage form
The method includes a dosage form that further comprises sodium lauryl sulfate.
Foil seal at the cap and desiccant pouches inside the bottle
The method further specifies that the bottle includes a foil seal at the cap and one or more desiccant pouches inside the bottle.
Across the independent claim and its refinements, the claim coverage centers on packaging a 50 mg diclofenac potassium rapid-bioavailability tablet using a formulation defined by water-soluble alkali metal carbonate or bicarbonate excipients plus hygroscopic diluent and freely soluble diluent in a specified ratio with defined water uptake behavior, combined with a moisture resistant bottle limiting moisture absorption under accelerated storage. Dependent claims further narrow rapid-bioavailability to specific tmax/Cmax and inter-subject variability criteria, require a single Cmax peak, and may add sodium lauryl sulfate and specific moisture-protection packaging elements such as a cap foil seal and desiccant pouches.
Stated Advantages
Improved rapid bioavailability preserved by preventing moisture uptake that otherwise softens tablets and degrades disintegration/dissolution performance.
Enables faster disintegration/dissolution linked to preserved moisture-protected tablet integrity.
Provides rapid-bioavailability performance targets using tmax/Cmax criteria and reduced inter-subject variability, including a single meaningful Cmax peak.
Improved moisture resistance by limiting moisture absorption of the dosage form during storage.
Documented Applications
Packaging a rapidly bioavailable diclofenac potassium tablet for acute pain medications.
Use of moisture resistant bottle packaging with moisture-protection components to maintain rapid-bioavailability tablet performance.
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