Bilastine Polymorphic Form 3 Tablet Stabilization

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Solution Overview

Problem

Current formulations of bilastine, particularly polymorphic form 3, face stability issues and inefficient dissolution, requiring additional chemical processing and excipients to achieve stable and effective pharmaceutical compositions for treating allergic rhino-conjunctivitis and urticaria.

Innovation Solution

Incorporating magnesium aluminometasilicate as a glidant and a water-soluble filler like mannitol or lactose in the bilastine tablets, which stabilizes polymorphic form 3, enhances dissolution properties, and prevents conversion to hydrate forms, thereby improving the stability and efficacy of the formulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If polymorphic form 3 of bilastine is used in tablet formulation, then dissolution properties are improved, but stability deteriorates due to conversion to hydrate forms during storage

Engineering Contradiction:
Improvedissolution rateVSAvoidpolymorph stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

Magnesium aluminometasilicate acts as an intermediary substance that prevents direct interaction between polymorphic form 3 and environmental moisture, thereby blocking the conversion pathway to hydrate forms while maintaining the high dissolution properties of form 3

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If additional chemical processing steps are implemented to stabilize polymorphic form 3, then stability is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvepolymorph stabilityVSAvoidmanufacturing process complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The stabilizing function is merged with the glidant excipient magnesium aluminometasilicate, which already serves flow and handling purposes in the formulation. This combination eliminates the need for separate stabilization steps or additional processing equipment

Inventive Principle:
Principle #5Merging (Combining)

3Ease of manufacture

If conventional excipients are used without magnesium aluminometasilicate, then formulation simplicity is maintained, but dissolution properties deteriorate

Engineering Contradiction:
Improveformulation simplicityVSAvoiddissolution rate
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

Magnesium aluminometasilicate performs multiple functions simultaneously: it acts as a glidant for powder flow, a stabilizer for polymorph maintenance, and a dissolution enhancer through its water-soluble filler properties, thereby improving dissolution without adding formulation complexity

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

The combination of magnesium aluminometasilicate and water-soluble fillers in bilastine tablets provides enhanced stability and complete drug release, comparable to commercial reference products, with improved disintegration and dissolution profiles, reducing the need for further chemical processing and maintaining stability over time.

Implementation Method 1

magnesium aluminometasilicate stabilizes polymorphic form 3, prevents conversion to hydrate forms

Methodology Applied
Scientific EffectPolymorph stabilization:

Implementation Method 2

enhances dissolution properties, complete drug release

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentEP3470062B1Pharmaceutical tablet composition comprising bilastine polymorphic form 3 and magnesium aluminometasilicate
Publication Date: 2020.10.28 ALFRED E TIEFENBACHER (GMBH & CO KG)
  • EP3470062B1 patent drawingFigure 1
  • EP3470062B1 patent drawingFigure 2
  • EP3470062B1 patent drawingFigure 3

AI summary

The invention relates to a pharmaceutical composition in the form of a tablet, comprising bilastine and magnesium aluminometasilicate. The invention further relates to a method of preparing a pharmaceutical composition in the form of a tablet comprising dry granulation of a blend of the tablet components and compression of the granules to a tablet, or direct compression of a blend to a tablet. The invention relates further to the medical use of the pharmaceutical composition in the treatment of allergic rhino-conjunctivitis and/or urticaria.