Effervescent Granules for Waterless Phosphate Binding

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Solution Overview

Problem

Patients with renal insufficiency, especially dialysis patients, face challenges in taking large amounts of phosphate binders due to their cumbersome form, unpleasant taste, and the need for excessive water intake, which affects compliance and dosing accuracy.

Innovation Solution

A pharmaceutical composition in the form of free-flowing granules or chewable tablets containing a phosphate-binding substance and an effervescent agent, which can be taken orally without water, providing a pleasant mouthfeel and precise dosage, using a combination of calcium acetate and magnesium carbonate to reduce the risk of hypercalcemia and utilizing effervescent agents to stimulate saliva production and mask taste.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If patients take large amounts of phosphate binders in traditional tablet form, then the phosphate binding effect is achieved, but the compliance and ease of operation deteriorate due to the large number of tablets and difficulty in swallowing

Engineering Contradiction:
Improvephosphate binding effectVSAvoidcompliance and ease of taking
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention divides the large number of traditional phosphate binder tablets into a smaller number of granules, each containing a precise dose of the active ingredient. This segmentation allows the total daily dose to be administered in fewer, easier-to-swallow units while maintaining the required phosphate binding effect.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the physical form of the phosphate binder from large tablets to small granules, and modifies the dosage parameters by pre-determining the exact amount of active ingredient in each granule. This parameter change enables easier swallowing and improved compliance while ensuring accurate dosing.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If patients are instructed to take phosphate binders with water, then the tablets can be swallowed easily, but the water intake increases which is harmful for renal insufficiency patients

Engineering Contradiction:
Improveease of swallowingVSAvoidexcessive water intake
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The invention changes the physical parameters of the dosage form by creating granules with specific size, shape, and surface properties that enable them to be swallowed easily with minimal or no water. The granule design allows for dry swallowing or swallowing with only a small amount of water, thus reducing the harmful fluid intake for renal patients.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If phosphate binders are administered in conventional forms, then the dosage can be controlled, but the unpleasant taste and poor mouthfeel reduce patient compliance

Engineering Contradiction:
Improvedosage controlVSAvoidpatient compliance
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention changes the sensory parameters of the phosphate binder by controlling the granule size, shape, and surface characteristics to improve mouthfeel and reduce unpleasant taste. The granule formulation provides a more acceptable sensory experience while maintaining precise dosage control through pre-determined active ingredient content.

Inventive Principle:
Principle #35Parameter changes

4Device complexity

If the phosphate binder is made into larger tablets to reduce the number of tablets, then the ease of operation improves, but the difficulty of swallowing and compliance worsens

Engineering Contradiction:
Improvenumber of tabletsVSAvoiddifficulty of swallowing
Core Design Contradiction:
Device complexityVSEase of operation

Solution Approach 1:

Instead of creating fewer large tablets, the invention segments the dosage into a moderate number of small granules. This segmentation approach finds an optimal balance between reducing the total number of units to be taken and maintaining a size that is easy to swallow, thereby improving compliance without compromising dosing frequency.

Inventive Principle:
Principle #1Segmentation

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

Enables easy and accurate administration of phosphate binders without additional water intake, improving patient compliance and reducing the risk of adverse effects like hypercalcemia, while providing a pleasant oral experience.

Implementation Method 1

contains an effervescent agent which contains an alkali or alkaline earth metal carbonate or an alkali or alkaline earth metal bicarbonate and a solid, organic, edible acid or its acidic salt

Methodology Applied
Scientific EffectEffervescence: Chemical Bonding

Implementation Method 2

The phosphate binders should be taken with meals in order to bind the phosphate contained in food in the intestine in the form of poorly soluble salts or non-absorbable complexes

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentEP2627313B1Phosphate binder formulation for simple ingestion
Publication Date: 2018.09.12 FRESENIUS MEDICAL CARE DEUTSCHLAND GMBH

AI summary

The invention relates to a pharmaceutical composition in the form of a free-flowing granulate or a chewable tablet, containing at least one phosphate-binding substance and at least one effervescent agent which contains a carbonate and a solid organic edible acid or the acidic salt thereof, for use in the treatment of hyperphosphataemia in patients suffering from renal insufficiency, wherein the granulate is applied orally without the addition of water.