Multiparticulate Differential Release Capsule for Hypertension

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Solution Overview

Problem

Current pharmaceutical compositions for treating heart conditions, specifically arterial hypertension, often require multiple drug administrations and can cause side effects like edema, and there is a lack of formulations combining losartan, amlodipine, and hydrochlorothiazide for simultaneous and controlled release.

Innovation Solution

A solid pharmaceutical composition of losartan potassium, amlodipine besylate, and hydrochlorothiazide in a multiparticulate form with controlled sequential release, utilizing enteric barriers and specific coatings for immediate and extended release, packaged in a hard gelatin capsule for synergistic therapeutic effects and reduced side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple drugs are administered separately to treat arterial hypertension, then each drug can be optimized for its specific mechanism of action, but the patient requires multiple administrations and experiences increased side effects such as edema

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidadministration convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent combines three antihypertensive drugs (losartan potassium, amlodipine besylate, and hydrochlorothiazide) into a single pharmaceutical composition with differentiated release profiles. This merging allows simultaneous administration of multiple drugs with different mechanisms of action while maintaining their individual therapeutic effects and reducing the burden of multiple separate administrations

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The pharmaceutical composition is segmented into different release compartments: an immediate-release portion containing losartan potassium and amlodipine besylate for rapid antihypertensive effect, and a delayed-release portion containing hydrochlorothiazide for subsequent diuretic action. This segmentation enables optimized timing of each drug's release to maximize therapeutic effectiveness

Inventive Principle:

Principle #1Segmentation

2Reliability

If amlodipine is used as a calcium channel blocker for hypertension treatment, then peripheral resistance is reduced and arterial pressure decreases, but edema and other side effects occur

Engineering Contradiction:

Improveantihypertensive effectVSAvoidedema and side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by including hydrochlorothiazide in the composition, which counteracts the edema-forming tendency of amlodipine. The delayed-release mechanism ensures that hydrochlorothiazide is released after amlodipine has exerted its vasodilatory effect, preemptively addressing the potential harmful effect of edema through diuretic action

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the harmful effect of amlodipine-induced edema into a benefit by strategically combining it with hydrochlorothiazide, a diuretic that promotes fluid excretion. The differentiated release timing ensures that the diuretic effect follows the vasodilatory effect, transforming the potential harm into a therapeutic advantage by reducing peripheral edema

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Speed

If losartan potassium and amlodipine besylate are released immediately, then rapid antihypertensive effect is achieved, but the diuretic effect of hydrochlorothiazide is needed at a later time to avoid interference

Engineering Contradiction:

Improveonset of actionVSAvoidtherapeutic effect optimization

Core Design Contradiction:

SpeedVSReliability

Solution Approach 1:

The pharmaceutical composition is divided into distinct release compartments: an immediate-release section containing losartan potassium and amlodipine besylate for rapid onset of antihypertensive action, and a delayed-release section containing hydrochlorothiazide that releases several hours later to provide diuretic effect without interfering with the initial vasodilatory and receptor-blocking actions

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent implements periodic action through differentiated release kinetics, where losartan potassium and amlodipine besylate are released immediately to produce rapid hemodynamic effects, while hydrochlorothiazide is released in a delayed periodic manner to provide sustained diuretic action at a different temporal phase, optimizing the overall therapeutic effect throughout the dosing interval

Inventive Principle:

Principle #19Periodic action

Data Source

PatentEP2883546B1New differential-release pharmaceutical composition containing three active principles

Publication Date: 2021.09.08 LANDSTEINER SCI DE C V

Figure 1

AI summary

This invention relates to a differential release formulation containing an angiotensin-II receptor antagonist, a calcium channel blocker and a diuretic, wherein the said pharmaceutical composition allows the sequential administration of the active principles in a single dose based on the treatment needs.