Crystalline Inhalable Powder Composition for Low Hygroscopicity

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Solution Overview

Problem

Amorphous powder compositions exhibit high hygroscopicity, agglomeration, and reduced shelf life when exposed to humid conditions, requiring hermetic packaging and complex inhaler devices to maintain stability and delivery efficacy.

Innovation Solution

Forming crystalline dry powder particles with a solid alkaloid salt and sugar alcohols like erythritol or myo-inositol, using spray drying or freeze drying methods to create a stable composition with low hygroscopicity and agglomeration resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If amorphous powder compositions are used, then water solubility is improved, but hygroscopicity increases and shelf life is reduced

Engineering Contradiction:
Improvewater solubilityVSAvoidshelf life
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the physical state parameter of the powder composition from amorphous to crystalline. This parameter change fundamentally alters the molecular arrangement and reduces water absorption capability while maintaining solubility benefits, directly resolving the contradiction between water solubility and shelf life.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite crystalline system combining multiple components (nicotine salt, sugar alcohol, amino acid) in a crystalline matrix. This composite approach allows the formulation to achieve both high water solubility through the soluble components and low hygroscopicity through the crystalline structure, simultaneously satisfying both requirements.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If amorphous powder compositions are used, then water solubility is improved, but agglomeration increases under humid conditions

Engineering Contradiction:
Improvewater solubilityVSAvoidagglomeration resistance
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter from amorphous to crystalline, which fundamentally alters how the material interacts with moisture. The crystalline structure prevents the sticky, agglomerated state that occurs in amorphous forms under humidity, while maintaining the water solubility needed for lung absorption.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent incorporates hydrophobic components and establishes a crystalline structure beforehand that acts as a protective barrier against moisture absorption. This pre-established protective structure prevents agglomeration from occurring in the first place when exposed to humid conditions during storage or handling.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Reliability

If hermetic packaging is used to maintain stability, then shelf life is improved, but device complexity and cost increase

Engineering Contradiction:
ImprovestabilityVSAvoidpackaging complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The crystalline powder composition is self-stabilizing and does not require hermetic packaging to maintain its properties. The intrinsic low hygroscopicity of the crystalline form allows the product to remain stable in ordinary packaging, eliminating the need for complex hermetic sealing systems and reducing both device complexity and cost.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

By changing from amorphous to crystalline form, the patent fundamentally alters the moisture interaction parameter, transforming the material from one that requires protective packaging to one that is inherently stable in ordinary packaging conditions.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If hermetic packaging is used, then moisture absorption is prevented, but productivity is reduced due to handling complexity

Engineering Contradiction:
Improvemoisture protectionVSAvoidhandling efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The crystalline composition provides self-protection against moisture through its intrinsic low hygroscopicity, eliminating the need for complex hermetic packaging systems that complicate handling and reduce productivity.

Inventive Principle:
Principle #25Self-service

5Reliability

If complex inhaler devices are used to separate humidity, then delivery efficacy is improved, but device complexity and cost increase

Engineering Contradiction:
Improvedelivery efficacyVSAvoidinhaler complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The crystalline powder composition delivers itself efficiently without requiring complex humidity separation mechanisms in the inhaler device. The inherent stability and low moisture absorption allow simple inhaler designs to achieve effective drug delivery.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The change from amorphous to crystalline form fundamentally changes the moisture interaction parameter, allowing the use of simple inhaler devices without complex humidity control mechanisms while maintaining effective delivery.

Inventive Principle:
Principle #35Parameter changes

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 crystalline particles maintain stability and long shelf life, reducing water absorption and agglomeration, and enable efficient inhalation delivery without complex packaging or devices.

Implementation Method 1

combining the alkaloid, sugar alcohol, and optionally an amino acid to form a liquid mixture, and spray drying or freeze drying the liquid mixture to form crystalline dry powder particles

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

combining the alkaloid, sugar alcohol, and optionally an amino acid to form a liquid mixture, and spray drying or freeze drying the liquid mixture to form crystalline dry powder particles

Methodology Applied
Scientific EffectFreezing: Freezing

Data Source

PatentEP4208152B1Low hygroscopicity active powder compositions
Publication Date: 2025.07.16 PHILIP MORRIS PRODUCTS SA
  • EP4208152B1 patent drawingFigure 1~2
  • EP4208152B1 patent drawingFigure 3~4
  • EP4208152B1 patent drawingFigure 5~6

AI summary

An inhalable powder includes crystalline dry powder particles. The crystalline dry powder particles include a solid salt of an alkaloid and a sugar alcohol. The salt is solid at 25 °C. The sugar alcohol may include mannitol, erythritol, myo-inositol, adonitol, xylitol, or a combination thereof. The inhalable powder may be part of a powder system that further includes a second population of particles having a particle size greater than that of the crystalline dry powder particles.