Modified Release Amoxicillin Product for Extended Plasma Levels

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Solution Overview

Problem

Current amoxicillin dosing regimens, particularly in immediate release formulations, require frequent administrations throughout the day, which can be inconvenient and may not maintain effective antibiotic levels for extended periods, while modified release formulations aim to address this but often do not achieve optimal pharmacokinetic profiles.

Innovation Solution

Development of an amoxicillin product with a modified release component that achieves specific partial AUC ratios, ensuring a prolonged and controlled release of the antibiotic, with a ratio of amoxicillin concentrations in different time intervals post-administration, maintaining effective plasma levels for a longer duration without exceeding maximum absorption limits.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If immediate release formulations are used, then the antibiotic is quickly absorbed and reaches peak concentration, but frequent administrations are required throughout the day

Engineering Contradiction:
Improveabsorption speedVSAvoidduration of effective plasma levels
Core Design Contradiction:
SpeedVSDuration of action of moving object

Solution Approach 1:

The amoxicillin dose is segmented into multiple release components: an immediate release component for rapid initial absorption and one or more modified release components for sustained release. This segmentation allows the formulation to achieve both quick peak concentration and prolonged therapeutic levels, eliminating the need for frequent dosing while maintaining effective plasma concentrations throughout the day.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The formulation employs periodic release patterns through modified release components that release amoxicillin in controlled intervals. The release profile is designed to provide an initial rapid release followed by sustained periodic release, maintaining therapeutic plasma levels over extended periods without requiring multiple daily administrations.

Inventive Principle:
Principle #19Periodic action

2Duration of action of moving object

If modified release formulations are used, then the duration of action is extended, but optimal pharmacokinetic profiles are not achieved

Engineering Contradiction:
Improveduration of antibiotic presenceVSAvoidpharmacokinetic profile optimization
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

Different components of the formulation have different release qualities tailored to specific needs: the immediate release component provides rapid initial absorption for quick therapeutic effect, while the modified release components provide sustained release for prolonged action. This local differentiation of release properties within a single formulation achieves optimal pharmacokinetic profiles that neither pure immediate nor pure modified release formulations can achieve alone.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The formulation is a composite pharmaceutical system combining immediate release and modified release components in specific ratios and configurations. This composite approach integrates the advantages of both release types, creating a formulation that achieves superior pharmacokinetic profiles with extended duration of action while maintaining reliable and predictable drug release patterns.

Inventive Principle:
Principle #40Composite materials

3Reliability

If multiple administrations are required, then effective antibiotic levels can be maintained, but patient compliance decreases

Engineering Contradiction:
Improvemaintenance of effective levelsVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The modified release components ensure continuous release of amoxicillin over an extended period, maintaining effective plasma concentrations without interruption. This continuous action allows the drug to be administered less frequently (e.g., once or twice daily instead of three or four times), significantly improving patient compliance while reliably maintaining therapeutic levels throughout the dosing interval.

Inventive Principle:
Principle #20Continuity of useful action

Data Source

PatentUS8778924B2Modified release amoxicillin products
Publication Date: 2014.07.15 SHIONOGI INC

AI summary

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.