Doxycycline Tablet with Segmented Release for Reduced Food Effect

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Solution Overview

Problem

Commercially available doxycycline capsules for rosacea treatment exhibit a significant food effect, requiring patients to take the medication on an empty stomach, which complicates patient convenience and compliance.

Innovation Solution

A once-daily tablet formulation of doxycycline with a reduced food effect, comprising a combination of immediate-release and controlled-release portions, allowing for administration with or without food, thereby minimizing the impact of food on drug absorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If doxycycline is administered in immediate-release capsule form, then the drug is rapidly absorbed, but the food effect significantly decreases Cmax and AUC0-t

Engineering Contradiction:
Improveabsorption rateVSAvoidbioavailability consistency
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The doxycycline dosage is divided into two distinct release portions: an immediate-release portion (50-95% of total dose) for rapid absorption and a controlled-release portion (5-50% of total dose) for sustained release. This segmentation allows the drug to achieve both rapid initial absorption and sustained release over time, reducing the impact of food on overall bioavailability while maintaining therapeutic efficacy.

Inventive Principle:
Principle #1Segmentation

2Reliability

If patients take doxycycline on an empty stomach to avoid food effect, then bioavailability is improved, but patient convenience and compliance deteriorate

Engineering Contradiction:
ImprovebioavailabilityVSAvoiddosing convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention changes the release rate parameter of doxycycline by incorporating a controlled-release portion that releases the drug slowly over time. This parameter change allows the medication to maintain effective plasma concentrations even when taken with food, thereby improving patient convenience and compliance without sacrificing bioavailability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If a higher dose of doxycycline is administered to overcome food effect, then therapeutic levels may be achieved, but the risk of side effects and toxicity increases

Engineering Contradiction:
Improvetherapeutic effectVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The controlled-release portion provides continuous release of doxycycline over an extended period, maintaining steady plasma concentrations. This continuous action ensures therapeutic efficacy without requiring high peak doses, thereby reducing the risk of side effects and toxicity associated with higher immediate doses.

Inventive Principle:
Principle #20Continuity of useful action

4Device complexity

If doxycycline is formulated as a single immediate-release dose, then the formulation is simple, but the duration of action is insufficient for once-daily dosing

Engineering Contradiction:
Improveformulation simplicityVSAvoiddrug action duration
Core Design Contradiction:
Device complexityVSDuration of action of moving object

Solution Approach 1:

The tablet is segmented into two functional portions with different release characteristics: an immediate-release portion for rapid onset and a controlled-release portion for extended duration. This segmentation achieves once-daily dosing capability while maintaining relative formulation simplicity through a single oral administration.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS9463196B2Pharmaceutical composition of doxycycline with reduced food effect
Publication Date: 2016.10.11 SUN PHARMACEUTICAL INDUSTRIES LTD

AI summary

The present invention relates to a once daily tablet comprising doxycycline at sub-antibiotic dose and one or more pharmaceutically acceptable excipients, wherein the tablet exhibits a reduced food effect. The invention further provides a method of treatment of rosacea by administering to a person in need thereof the doxycycline tablet with or without food. A process of preparing the tablet is also provided.