Sequential Enteric-Coated Aspirin and COX-2 Inhibitor Delivery

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Solution Overview

Problem

Current drug formulations for COX-2 inhibitors and aspirin have limitations in absorption rates and solubility, leading to gastrointestinal side effects and cardiovascular risks, particularly when used together for conditions like osteoarthritis, chronic pain, and migraines, due to rapid absorption in the stomach and poor solubility in the small intestine.

Innovation Solution

A method involving enteric or partial enteric coatings for sequential administration of aspirin or aspirin derivatives and COX-2 inhibitors to target bioabsorption in the small intestine or colon, reducing gastrointestinal side effects by controlling the release and absorption in specific areas of the GI tract, using pH-sensitive, time-sensitive, or microflora-activated coatings.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aspirin and COX-2 inhibitor are administered together in conventional formulations, then the therapeutic effect is achieved, but gastrointestinal side effects increase and absorption rates are suboptimal

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

Solution Approach 1:

The patent divides the GI tract into multiple absorption zones (stomach, small intestine, colon) and assigns different drugs to different zones using enteric coatings with specific dissolution characteristics. Aspirin is formulated for rapid absorption in the stomach while COX-2 inhibitor is designed for delayed absorption in the small intestine or colon, thereby segmenting the absorption process to reduce GI side effects while maintaining therapeutic efficacy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies different enteric coating properties to different drugs within the same formulation. The aspirin component has coatings optimized for rapid dissolution in the acidic stomach environment, while the COX-2 inhibitor component has coatings designed to resist stomach acid and dissolve in the neutral or alkaline environment of the small intestine or colon. This local differentiation of coating properties enables targeted absorption and reduces GI harm.

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If COX-2 inhibitor is administered with poor solubility in the small intestine, then the drug can be delivered to the target site, but absorption rate decreases

Engineering Contradiction:
Improvedrug delivery to target siteVSAvoidabsorption rate
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

The patent uses enteric coatings as intermediary substances that mediate the delivery and release of the COX-2 inhibitor. These coatings act as protective barriers that resist dissolution in the stomach (acidic environment) and only dissolve in the neutral or alkaline environment of the small intestine or colon, thereby controlling the timing and location of drug release to improve absorption rate while maintaining targeted delivery.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes pH-dependent dissolution characteristics of enteric coatings to control drug release. By selecting coatings with specific pH dissolution ranges, the formulation ensures that the COX-2 inhibitor remains protected in the acidic stomach environment and is released only when the pH changes in the small intestine or colon, thereby optimizing absorption parameters for this poorly soluble drug.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If enteric coating is applied to control drug release in the small intestine or colon, then gastrointestinal side effects are reduced, but formulation complexity increases

Engineering Contradiction:
Improvegastrointestinal side effectsVSAvoidformulation complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent combines multiple enteric-coated drug components into a single multi-component formulation that can be administered as one unit. The formulation integrates aspirin and COX-2 inhibitor with different enteric coating properties, allowing both drugs to be delivered with controlled release characteristics while reducing the number of separate dosing events and simplifying patient compliance.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent develops enteric coating systems that serve multiple functions simultaneously: protecting the drug from stomach acid, controlling the timing of release, directing absorption to specific GI regions, and reducing GI side effects. This multi-functionality of the coating system reduces the need for additional formulation components and simplifies the overall design.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enhances bioavailability, reduces gastrointestinal side effects and cardiovascular risks, and provides effective treatment for chronic inflammation, migraines, and pre-cancerous polyps by optimizing drug absorption in targeted areas of the GI tract, while maintaining the cardiovascular benefits of low-dose aspirin.

Implementation Method 1

at least one of which has an enteric or partial enteric coating for bioabsorption in a patient's small intestine or colon

Methodology Applied
Scientific EffectEnteric coating: Coatings

Implementation Method 2

using pH-sensitive, time-sensitive, or microflora-activated coatings

Methodology Applied
Scientific EffectpH-sensitive:

Implementation Method 3

using pH-sensitive, time-sensitive, or microflora-activated coatings

Methodology Applied
Scientific Effecttime-sensitive:

Implementation Method 4

using pH-sensitive, time-sensitive, or microflora-activated coatings

Methodology Applied
Scientific Effectmicroflora-activated:

Implementation Method 5

The solubility characteristics of spray dried amorphous dispersions of drugs are enhanced

Methodology Applied
Scientific EffectSpray dried dispersion:

Data Source

PatentUS20230320992A1Sequential administration of partitioned absorption aspirin or active aspirin derivative and cox-2 inhibitor
Publication Date: 2023.10.12 CELSPRIN

AI summary

Described herein are an aspirin or active aspirin derivative and a COX-2 inhibitor, at least one of which has an enteric or partial enteric coating, administered in combination yet delivered sequentially, for the treatment and prophylactic treatment of diseases, symptoms and conditions. In some embodiments, the COX-2 inhibitor has the enteric coating; however, the aspirin or active aspirin derivative may additionally or alternately have the enteric coating. In all embodiments, the drug having the enteric coating or enteric formulation is targeted for absorption in the small intestine or colon, or both the small intestine and the colon.