Inhalable Medicament Solution Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Active ingredients used in inhalation therapy, such as tiotropium, ipratropium, and others, are susceptible to chemical degradation when formulated as solutions, particularly due to hydrolysis and solvolysis, leading to instability and reduced efficacy.
Innovation Solution
Incorporating a magnesium or calcium salt, such as magnesium chloride, in a solution formulation at a concentration of 0.0001 to 0.01 wt% based on the total weight, which stabilizes the active ingredients and prevents chemical degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If active ingredients are formulated as solution formulations, then ease of manufacture and delivery efficiency are improved, but chemical stability deteriorates due to hydrolysis and solvolysis
Solution Approach 1:
Magnesium or calcium salts are introduced as intermediary substances that mediate between the active ingredient and the liquid phase. These salts form complexes with the active ingredient, creating a protected state that prevents direct interaction with water or alcohol molecules that would cause hydrolysis or solvolysis, thereby maintaining chemical stability in solution formulations
Solution Approach 2:
The chemical environment parameters of the liquid phase are modified by adding magnesium or calcium salts. This changes the ionic composition and pH characteristics of the solution, creating conditions that suppress hydrolysis and solvolysis reactions while maintaining the active ingredient in dissolved form, thus preserving both ease of manufacture and chemical stability
2Productivity
If active ingredients are formulated as solution formulations, then delivery efficiency is improved, but chemical reactivity increases leading to degradation
Solution Approach 1:
Magnesium or calcium salts act as protective intermediaries that form stable complexes with the active ingredient. This complexation reduces the chemical reactivity of the active ingredient toward water and alcohol in the liquid phase, preventing degradation while maintaining the formulation in a deliverable solution state through aerosolisation
Solution Approach 2:
The magnesium or calcium salts provide beforehand protection by pre-complexing with the active ingredient before exposure to degrading conditions. This prior cushioning effect creates a stable chemical environment that buffers against hydrolysis and solvolysis during storage and delivery, ensuring the active ingredient reaches the target without degradation
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 addition of magnesium or calcium salts significantly enhances the chemical stability of the active ingredients, reducing degradation and maintaining their effectiveness in inhalation formulations, even in challenging environments like pressurized metered dose inhalers (pMDIs) with minimal impact on the canister material.
Implementation Method 1
a magnesium or calcium salt, dissolved in the liquid phase; wherein the amount of salt is from 0.0001 to 0.01 wt%, based on the total weight of the formulation, and wherein the active ingredient is selected from tiotropium, ipratropium, glycopyrronium, oxitropium, aclidinium, and trospium
Implementation Method 2
active ingredients susceptible to chemical degradation... susceptible to hydrolysis and/or solvolysis... The addition of magnesium or calcium salts significantly enhances the chemical stability of the active ingredients, reducing degradation
Data Source
Figure 1
AI summary
Accordingly, the present invention provides a solution formulation for inhalation comprising : a liquid phase; an active ingredient having a functional group which is susceptible to hydrolysis and/or solvolysis, dissolved in the liquid phase; and a magnesium or calcium salt, dissolved in the liquid phase. The formulation is particularly suited to pMDIs and nebulisers.