Calcium Carbonate and Sugar Alcohol Roller Compaction

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Solution Overview

Problem

Formulating chewable calcium tablets with a pleasant taste and acceptable mouthfeel is challenging due to the high dose of calcium required, poor compressibility of regular-shaped calcium carbonate, and inherent taste or chalkiness issues, along with the need for suitable excipients and sufficient taste masking.

Innovation Solution

The process of roller compaction is used to agglomerate calcium-containing compounds with pharmaceutically acceptable sugar alcohols, such as sorbitol and isomalt, to create a particulate material suitable for forming tablets with improved taste, mouthfeel, and compressibility, without the need for wet granulation, which allows for the incorporation of sensitive substances like vitamin D.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If high dose of calcium carbonate is used to meet therapeutic requirements, then the calcium content is sufficient, but the tablets have poor compressibility and unacceptable taste/mouthfeel

Engineering Contradiction:

Improvecalcium contentVSAvoidcompressibility

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent combines calcium carbonate particles with sugar alcohol particles (sorbitol, isomalt, or mannitol) to form composite granules. The sugar alcohol acts as a binding agent that improves compressibility while masking the chalky taste of calcium carbonate. This composite approach allows high calcium content (60-95% w/w) to be achieved while maintaining acceptable tablet compressibility and taste properties.

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If regular-shaped calcium carbonate is used, then the calcium delivery is effective, but the tabletting properties are poor requiring additional excipients

Engineering Contradiction:

Improvecalcium deliveryVSAvoidnumber of excipients

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent merges the calcium carbonate particles with sugar alcohol particles into a single granulated formulation. The sugar alcohol serves multiple functions: it acts as a binder to improve tabletting properties, a sweetener to mask chalky taste, and a flow agent. This merging reduces the need for separate excipients and simplifies the formulation while maintaining effective calcium delivery.

Inventive Principle:

Principle #5Merging (Combining)

3Object-affected harmful factors

If chewable tablets are formulated to mask taste, then the taste acceptability improves, but the tablet size increases making it inconvenient for patients

Engineering Contradiction:

Improvetaste maskingVSAvoidtablet size

Core Design Contradiction:

Object-affected harmful factorsVSLength of moving object

Solution Approach 1:

The patent changes the physical and chemical parameters of the formulation by using finely ground calcium carbonate (mean particle size 4-20 μm) combined with sugar alcohol in specific ratios (60:40 to 95:5 w/w). This parameter optimization allows effective taste masking with smaller tablet sizes, as the sugar alcohol provides sweetness and the fine particle size improves dissolution and masking efficiency.

Inventive Principle:

Principle #35Parameter changes

4Strength

If wet granulation is used to improve compressibility, then the tablet strength improves, but sensitive substances like vitamin D cannot be incorporated

Engineering Contradiction:

Improvetablet strengthVSAvoidincorporation of sensitive substances

Core Design Contradiction:

StrengthVSAdaptability or versatility

Solution Approach 1:

The patent replaces the wet granulation process (which uses liquid binders and prolonged mixing) with a dry granulation process where calcium carbonate and sugar alcohol are mechanically mixed and then compressed directly into tablets. This mechanical substitution eliminates the need for liquid moisture that could degrade sensitive substances like vitamin D, while still achieving adequate tablet strength through the compressible sugar alcohol matrix.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 method produces tablets with acceptable taste, mouthfeel, and crushing strength, maintaining the physiological efficacy of calcium while ensuring stability and suitability for use in high-humidity environments, and allows for the incorporation of sensitive active ingredients like vitamin D.

Implementation Method 1

The process involves agglomeration of the calcium-containing compound and the pharmaceutically acceptable sugar alcohol by means of roller compaction

Methodology Applied

Scientific EffectCompression: Compression

Data Source

PatentUS10357460B2Particulate comprising a calcium-containing compound and a sugar alcohol

Publication Date: 2019.07.23 TAKEDA AS

AI summary

The present invention relates to a particulate material and a solid dosage form notably tablets comprising a regularly shaped calcium-containing compound such as a calcium salt as a therapeutically and/or prophylactically active substance and a pharmaceutically acceptable sugar alcohol such as, e.g., sorbitol and/or isomalt that has a micro structure as evidenced by SEM. The invention also relates to a process for the preparation of the particulate material and solid dosage form. The process involves agglomeration of the calcium-containing compound and the pharmaceutically acceptable sugar alcohol by means of roller compaction. The particulate material obtained by roller compaction is suitable for use in the further processing of the particulate material into e.g. tablets such as chewing tablets.