Buffered Coated Can for pMDI pH Stability

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Solution Overview

Problem

Current pressurized metered dose inhalers (pMDIs) lack a practical method to maintain the apparent pH of formulations containing corticosteroids and long-acting beta agonists (LABAs) with hydrofluoroalkane (HFA) or hydrofluoroolefin (HFO) propellants, affecting stability, shelf life, and consistent medication delivery.

Innovation Solution

An internally coated can with materials like epoxy-phenol resin, perfluorinated polymers, and fluorinated-ethylene-propylene (FEP) coatings acts as a pH buffering system, stabilizing the apparent pH between 2.5 and 5, eliminating the need for external buffering agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If external buffering agents are added to stabilize pH, then pH stability is improved, but formulation complexity and potential degradation increase

Engineering Contradiction:
ImprovepH stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The invention extracts the buffering function from the bulk formulation and relocates it to the canister coating layer. The coating material (fluorinated polymer or epoxy-phenol resin) provides pH buffering capacity specifically at the interface where degradation occurs, eliminating the need for buffering agents throughout the entire formulation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The buffering action is localized to the canister interior surface where pH control is most critical for preventing degradation. The coating layer creates a localized buffering zone at the formulation-canister interface, providing pH stability exactly where it is needed without affecting the bulk formulation composition.

Inventive Principle:
Principle #3Local quality

2Ease of manufacture

If conventional can materials are used without coating, then manufacturing simplicity is maintained, but particle adhesion and deposition occur

Engineering Contradiction:
Improvemanufacturing simplicityVSAvoidparticle adhesion
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The invention uses composite material systems where fluorinated polymers or epoxy-phenol resins are applied as coating layers on conventional metal canisters. This composite structure combines the manufacturing simplicity of standard canister fabrication with the particle-repelling properties of the coating material.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The coating layer acts as an intermediary between the canister surface and the formulation. This intermediate layer prevents direct contact between the formulation particles and the canister surface, eliminating adhesion and deposition while maintaining manufacturing simplicity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If HFA propellants are used, then efficacy and compatibility are improved, but environmental harm increases

Engineering Contradiction:
Improvepharmaceutical compatibilityVSAvoidgreenhouse warming potential
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the chemical composition parameters of the canister coating material to provide pH buffering capacity that is specifically effective with HFA propellants. The fluorinated polymer or epoxy-phenol resin coating creates a chemical environment that maintains formulation stability and pH control when used with HFA propellants.

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 coated can maintains stable apparent pH over time, enhancing the stability and reproducibility of the formulation, ensuring consistent aerosol delivery and prolonged shelf life without additional buffering agents, while reducing greenhouse warming potential.

Implementation Method 1

the coated can acts as a pH buffering system, stabilizing the apparent pH between 2.5 and 5

Methodology Applied
Scientific EffectBuffer capacity:

Implementation Method 2

Fluorocarbon polymers are commonly used to coat the interior can surfaces of pMDIs to eliminate particle adhesion, or deposition on can walls

Methodology Applied
Scientific EffectAdhesion elimination:

Implementation Method 3

A pMDI device typically presents a medical-containing canister (or a 'can' as herein referred to), and an actuator housing having a mouthpiece... a propellant to expel droplets containing the pharmaceutical products to the respiratory tract as an aerosol

Methodology Applied
Scientific EffectAerosol formation: Aerosol

Data Source

PatentUS20230347080A1Pressured metered dose inhalers comprising a buffered pharmaceutical formulation
Publication Date: 2023.11.02 CHIESI FARMACEUTICI SPA

AI summary

The present invention generally relates to an aerosol formulation comprising formoterol and beclomethasone dipropionate, said formulation being contained in a coated can, particularly useful for the use in a pressurised metered dose inhaler for the treatment of respiratory diseases.