Atorvastatin Composition Direct Compression Stability

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Solution Overview

Problem

Atorvastatin salts used in solid pharmaceutical oral compositions have poor stability and solubility, leading to challenges in maintaining the active ingredient's quality and absorption rates due to their low solubility and dissolution rates.

Innovation Solution

A solid pharmaceutical oral composition comprising a crystalline form of atorvastatin salt with a particle size distribution of less than 100 µm, combined with hydroxypropylmethyl cellulose as a hydrogel former, which has a dynamic viscosity of 50 mPa s to 500 mPa s, allowing for direct pressing and enhanced stability and controlled active ingredient release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If atorvastatin salt is used in solid pharmaceutical oral composition, then the active ingredient can be delivered in solid form, but the stability and solubility are poor

Engineering Contradiction:

ImprovestabilityVSAvoidsolubility

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent changes the particle size parameter of the atorvastatin salt to D90 < 100 μm through micronization, which improves dissolution rate and solubility while maintaining stability in the solid compressed form

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite formulation by combining micronized atorvastatin salt with specific excipients including hydrogel formers and disintegrants, which together improve both stability and solubility/dissolution characteristics

Inventive Principle:

Principle #40Composite materials

2Productivity

If atorvastatin salt is used in solid pharmaceutical oral composition, then the active ingredient can be delivered in solid form, but the dissolution rate is low

Engineering Contradiction:

Improvedissolution rateVSAvoidstability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies micronization to reduce particle size (D90 < 100 μm), which increases the surface area and dissolution rate of the atorvastatin salt while maintaining its stability in the compressed tablet form

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary micronization of the atorvastatin salt before compression, preparing the active ingredient in advance with optimized particle size to ensure rapid dissolution upon administration while preserving stability during storage

Inventive Principle:

Principle #10Preliminary action

3Ease of manufacture

If granulation and solvent use are used in production, then the composition can be manufactured, but the production cost increases

Engineering Contradiction:

Improveproduction costVSAvoidproduction process

Core Design Contradiction:

Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent eliminates the granulation step and solvent usage from the manufacturing process by using direct compression technology, thereby reducing production costs and simplifying the production process while still achieving the desired product quality

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentEP3487484B1Atorvastatin composition

Publication Date: 2024.06.19 STADA ARZNEIMITTEL AG

AI summary

The invention relates to a solid pharmaceutical oral composition, comprising an atorvastatin salt in crystalline form as active ingredient, wherein the active substance has a particle size distribution with a D90 value of less than 100 µm. In order to further develop such a composition in such a way that the composition has a relatively high chemical stability with respect to the active ingredient, the composition, according to the invention, is directly pressed.