Tiotropium MDI Propellant Stability and GWP Reduction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Tiotropium-based formulations in metered dose inhalers (MDIs) face challenges with limited physical and chemical stability, particularly when exposed to excipients and solvents, leading to reduced shelf life and the need for refrigerated storage, and existing propellants like HFA-134a and HFA-227ea have high global warming potentials.
Innovation Solution
The use of 1,1-difluoroethane (HFA-152a) as a propellant in pharmaceutical compositions containing tiotropium, which improves chemical stability, aerosolization performance, and reduces global warming potential, while maintaining compatibility with standard MDI components.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If HFA-134a or HFA-227ea are used as propellants, then the pharmaceutical composition can be delivered via MDI, but the global warming potential increases
Solution Approach 1:
The patent changes the chemical parameter of the propellant from HFA-134a or HFA-227ea to HFA-152a, which has lower global warming potential. This parameter change resolves the contradiction by selecting a propellant with improved environmental properties while maintaining the required chemical stability for tiotropium formulations.
Solution Approach 2:
The patent adopts HFA-152a as a replacement propellant that offers shorter atmospheric lifetime and lower environmental persistence compared to HFA-134a and HFA-227ea, effectively treating the propellant as a shorter-living substance that degrades more quickly in the environment, thus reducing long-term harmful effects.
2Reliability
If tiotropium is formulated with conventional excipients and solvents, then the drug can be delivered, but the physical and chemical stability decreases
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using HFA-152a as the propellant medium, which provides improved chemical stability for tiotropium. This parameter change in the propellant system resolves the contradiction by creating a more stable environment for the drug, thereby extending shelf life without compromising delivery capability.
Solution Approach 2:
The patent creates a more inert chemical environment by using HFA-152a as the propellant, which exhibits lower reactivity with tiotropium compared to conventional excipients and solvents. This inert environment protects the drug from degradation, resolving the contradiction between deliverability and stability.
3Reliability
If refrigerated storage is implemented, then the chemical stability is maintained, but the ease of operation and patient convenience decreases
Solution Approach 1:
The patent changes the formulation parameters by using HFA-152a as the propellant, which inherently provides improved chemical stability that allows the product to be stored at ambient temperatures. This parameter change eliminates the need for refrigeration, resolving the contradiction by maintaining stability while improving storage convenience and patient ease of use.
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
HFA-152a propellant enhances the chemical stability and aerosolization performance of tiotropium formulations, maintaining effectiveness even after storage under stress conditions, and reduces the global warming potential compared to HFA-134a and HFA-227ea, allowing for a longer shelf life at ambient temperatures.
Implementation Method 1
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
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
Data Source
AI summary
A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one tiotropium compound selected from tiotropium, tiotropium bromide and tiotropium bromide monohydrate and at least one olodaterol compound selected from olodaterol and the pharmaceutically acceptable salts thereof; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a).