Coated Can pH Buffering for pMDI Formulation Stability

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current pressurized metered dose inhalers (pMDIs) lack an effective method to buffer the apparent pH of formulations containing corticosteroids, long-acting beta agonists (LABAs), and long-acting muscarinic antagonists (LAMAs), which affects stability, shelf life, and consistent medication delivery.

Innovation Solution

An internally coated can with a dedicated metering valve system, utilizing coatings such as epoxy-phenol resin or perfluorinated polymers, acts as a pH buffering system, maintaining the apparent pH between 2.5 and 5, eliminating the need for external buffering agents and enhancing stability and aerosolizing performance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If traditional pMDI formulations are used without internal coating, then the device structure is simpler, but the apparent pH cannot be buffered and formulation stability deteriorates

Engineering Contradiction:
Improveformulation stabilityVSAvoiddevice structure
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The can is pre-coated with fluorocarbon polymer before formulation insertion, creating a stable pH-buffering environment in advance. This preliminary coating action eliminates the need for complex external buffering systems and ensures formulation stability from the moment of assembly.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The fluorocarbon polymer coating acts as an intermediary layer between the metal can and the pharmaceutical formulation. This intermediate layer provides pH buffering capacity and protects the formulation from direct contact with the can walls, thereby stabilizing the composition without requiring structural modifications to the device.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If external buffering agents are added to the formulation, then pH control is improved, but the formulation complexity and potential for degradation products increase

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

Solution Approach 1:

The pH buffering function is extracted from the formulation itself and transferred to the can coating. By removing the need for buffering agents from the formulation, the invention simplifies the formulation composition while maintaining effective pH control through the fluorocarbon polymer coating.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The fluorocarbon polymer coating possesses inherent pH buffering capacity that allows it to self-regulate the apparent pH of the formulation without requiring external buffering agents. The coating serves itself as both the container lining and the pH control mechanism.

Inventive Principle:
Principle #25Self-service

3Productivity

If CFC propellants are used in pMDI, then the aerosolizing performance is optimized, but the environmental impact and global warming potential increase

Engineering Contradiction:
Improveaerosolizing performanceVSAvoidenvironmental impact
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the propellant parameter from CFC to HFA, adjusting the chemical composition to eliminate ozone-depleting substances while maintaining the aerosolizing performance required for effective drug delivery. This parameter change addresses environmental concerns without sacrificing therapeutic efficacy.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention converts the potential harm of propellant selection by using HFA propellants that, while still fluorinated, do not deplete the ozone layer. The regulatory pressure from environmental concerns is converted into a benefit by driving innovation toward more sustainable propellant options that maintain device performance.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 with a dedicated valve system stabilizes the apparent pH of pMDI formulations over time, ensuring the stability and reproducibility of the formulation, while reducing greenhouse warming potential and maintaining optimal chemical conditions within the device.

Implementation Method 1

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

Methodology Applied
Scientific EffectAdhesion prevention: Hydrophobe

Implementation Method 2

pMDI devices may use a propellant to expel droplets containing the pharmaceutical products to the respiratory tract as an aerosol

Methodology Applied
Scientific EffectAerosol generation: Aerosol

Implementation Method 3

Pressurized metered dose inhalers (pMDIs) are well known devices for administering pharmaceutical products to the respiratory tract by inhalation

Methodology Applied
Scientific EffectPressure-driven flow: Pressure Gradient

Implementation Method 4

the possibility to have an alternative class of propellant and alternative means for obtaining effective pMDI devices are always under consideration... the apparent pH and the water content of the formulation nebulized by said device

Methodology Applied
Scientific EffectpH buffering:

Data Source

PatentUS20230080276A1Pressurised metered dose inhalers comprising a buffered pharmaceutical formulation
Publication Date: 2023.03.16 CHIESI FARMACEUTICI SPA

AI summary

The present invention generally relates to an aerosol formulation comprising formoterol, beclomethasone dipropionate and glycopyrronium bromide, 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.