Modified release amoxicillin products
Inventors
Flanner, Henry H. • Tolle-Sander, Sanna • Treacy, Donald • Burnside, Beth A. • Clausen, Susan P.
Assignees
Publication Number
US-8778924-B2
Publication Date
2014-07-15
Expiration Date
2026-12-04
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Abstract
An amoxicillin product comprising: at least one modified release component(s), wherein the at least one modified release component(s) comprises at least amoxicillin and a pharmaceutically acceptable carrier; and wherein when administered to a patient or subject in the fed state said amoxicillin product exhibits a pharmacokinetic profile for amoxicillin in the plasma characterized as follows: (1) the ratio of the portion of the AUC as measured from 2 hours post-administration to 5 hours post-administration to the portion of the AUC as measured from administration to 2 hours post-administration is at least 2.0:1; and (2) the ratio of the portion of the AUC as measured from 5 hours post-administration to 12 hours post-administration to the portion of the AUC as measured from administration to 2 hours post-administration is at least 1.1:1.
Core Innovation
The invention relates to an amoxicillin product that includes at least one modified release component comprising at least amoxicillin and a pharmaceutically acceptable carrier. This product is specifically formulated so that, when administered to a patient in the fed state, it produces a pharmacokinetic profile of amoxicillin in the plasma characterized by defined partial area under the curve (AUC) ratios: the ratio of AUC measured from 2–5 hours post-administration to that from 0–2 hours is at least 2.0:1, and the ratio of AUC from 5–12 hours to 0–2 hours is at least 1.1:1.
The problem addressed is the need for improved amoxicillin dosing regimens. Conventional immediate release (IR) formulations often require multiple doses per day (e.g., twice-a-day (b.i.d.), three times daily (t.i.d.), or four times daily (q.i.d.)) to maintain effective plasma concentrations, leading to inconvenience and adherence issues. Modified release forms are available but may not provide optimal pharmacokinetics, especially in the fed state.
The invention encompasses products containing a mixture of immediate release and one or more modified release components, such as delayed release and/or sustained release forms. These components are engineered to release amoxicillin at different times, producing the targeted AUC ratios. The formulations can be in the form of tablets, capsules, sprinkles, or liquid suspensions, and may be administered once or twice daily, maintaining effective amoxicillin plasma levels in a convenient regimen.
Claims Coverage
There is one independent claim that defines the primary inventive feature of the patent.
Once-a-day amoxicillin product with specific multi-component release profile
An amoxicillin product comprising an immediate release component and at least one modified release component, specifically: - A first delayed release component with amoxicillin coated with methacrylic acid copolymer dispersion, initiating release after the immediate release component. - A second delayed release component with amoxicillin coated with methacrylic acid copolymer dispersion and hypromellose acetate succinate, initiating release after the first delayed release component. - The product, when administered as a single dose in the fed state, yields the following pharmacokinetic partial AUC ratios: (a) AUC(2–5)/AUC(0–2) of at least 2.0:1 and (b) AUC(5–12)/AUC(0–2) of at least 1.1:1. - The product is a once-a-day amoxicillin product. - The specified AUC ratios do not exceed 10:1.
The inventive feature provides an amoxicillin product having immediate and sequential delayed release components, engineered to produce distinctive partial AUC plasma profiles when dosed once daily, notably in the fed state.
Stated Advantages
Allows for once-a-day or twice-a-day dosing of amoxicillin, reducing the frequency of administration required for effective plasma concentrations.
Provides targeted partial AUC pharmacokinetic profiles, maintaining amoxicillin levels in plasma over a prolonged period.
The extent of absorption (AUCo-inf) of the formulation is at least 75%, and preferably at least 80%, of that of an immediate release amoxicillin product.
Equivalent extent of absorption can be achieved whether the product is administered in the fed or fasted state.
Documented Applications
Treatment of various infections in humans caused by bacterial pathogens, including pharyngitis, tonsillitis, sinusitis, bronchitis, pneumoniae, ear infection (otitis media), uncomplicated skin and skin structure infections, and uncomplicated urinary infections.
Formulations can be used in combination with clavulanate or other beta-lactamase inhibitors, especially for treating infections involving beta-lactamase producing pathogens.
Applicable against a wide range of bacterial pathogens such as Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Klebsiella species, Moraxella catarrhalis, Neisseria gonorrhoeae, Proteus mirabilis, and others.
Specifically formulated to target tonsillopharyngitis secondary to Streptococcus pyogenes.
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