Salbutamol Inhaler Propellant Reducing GWP

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Solution Overview

Problem

There is a need for a pharmaceutical composition containing salbutamol that uses a propellant with reduced global warming potential (GWP) compared to HFA-134a and HFA-227ea, and also requires improved stability, especially for use in metered dose inhalers (MDIs).

Innovation Solution

A pharmaceutical composition comprising salbutamol base and a propellant component at least 90 weight % of 1,1-difluoroethane (HFA-152a), which exhibits improved chemical stability, low GWP, and compatibility with standard MDI components, including uncoated aluminum cans and valves, while maintaining the drug in a stable suspension or solution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If HFA-134a or HFA-227ea is used as propellant, then adequate propellant performance is achieved, but global warming potential is too high

Engineering Contradiction:
Improveglobal warming potentialVSAvoidpropellant performance
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the chemical composition parameters of the propellant by using HFA-152a (1,1-difluoroethane) instead of HFA-134a or HFA-227ea. This substitution maintains the necessary vapor pressure and boiling point characteristics for MDI operation while significantly reducing the global warming potential from GWP-1430 and GWP-3220 to a lower GWP value, thus resolving the contradiction between environmental harm and functional performance.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If HFA-152a is used as propellant, then global warming potential is reduced, but chemical stability may be compromised

Engineering Contradiction:
Improveglobal warming potentialVSAvoidchemical stability
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent employs HFA-152a as a propellant that is designed to be consumed during the product lifecycle. The propellant is contained in a sealed MDI canister and is intended to be used up over time (typically 120-240 doses). This approach allows the use of a lower GWP propellant without long-term stability concerns, as the propellant is replaced with each new canister, thus resolving the contradiction between reduced environmental harm and maintained chemical stability.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If water content is increased to improve drug solubility, then drug delivery is enhanced, but chemical stability deteriorates

Engineering Contradiction:
Improvedrug solubilityVSAvoidchemical stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent optimizes the water content parameter to a specific range (0.1-5% w/v) that balances drug solubility requirements with chemical stability constraints. By precisely controlling water content within this narrow window, the formulation achieves adequate dissolution of salbutamol base while preventing excessive water from promoting degradation reactions, thus resolving the contradiction between solubility enhancement and stability maintenance.

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 use of HFA-152a as a propellant in salbutamol-containing compositions enhances chemical stability and aerosolization performance, reducing GWP and maintaining effective drug delivery even after storage, with improved fine particle fraction retention.

Implementation Method 1

it needs to have a number of properties. These include an appropriate boiling point and vapour pressure so that it can be liquefied in a closed container at room temperature but develop a high enough pressure when the MDI is activated to deliver the drug as an atomised formulation

Methodology Applied
Scientific EffectLiquefaction: Condensation

Implementation Method 2

The propellant should also be capable of maintaining the drug in a homogeneous solution, in a stable suspension or in a stable dispersion for a sufficient time to permit reproducible delivery of the drug in use

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentEP3787598B1Pharmaceutical composition comprising salbutamol
Publication Date: 2022.04.13 MEXICHEM FLUOR S A DE CV

AI summary

A pharmaceutical composition is described. The composition comprises; (i) a drug component comprising salbutamol; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a).