Inorganic Acid Mixture Stabilizes LABA in Aluminum pMDI Canisters
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Solution Overview
Problem
Existing pharmaceutical compositions for pressurized metered dose inhalers (pMDIs) face challenges in maintaining the stability of LABA agents, LAMA agents, and corticosteroids over an extended product lifetime, especially when stored in aluminum canisters, which affects the consistency and efficacy of respiratory disease treatment.
Innovation Solution
A pharmaceutical composition comprising a LABA agent, a co-solvent, a propellant, and a mixture of at least two inorganic acids, specifically HCl and H3PO4, which stabilizes the formulation and maintains its stability even in aluminum canisters, comparable to the stability achieved with FEP technology.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If a single acid (HCl) is used in the formulation, then the stability is improved compared to no acid, but the stability is insufficient for extended product lifetime and requires FEP coated cans
Solution Approach 1:
The patent combines multiple inorganic acids (HCl and H3PO4) into a single formulation system. This merging of acid components creates a synergistic effect that provides superior stability compared to using HCl alone, thereby eliminating the need for FEP coated cans and allowing the use of simpler aluminum canisters.
Solution Approach 2:
The formulation uses a composite acid system comprising HCl and H3PO4 in specific proportions. This composite approach leverages the complementary properties of both acids to achieve enhanced stability profiles, resolving the contradiction between formulation stability and device complexity.
2Stability of the object's composition
If FEP coated canisters are used to maintain stability, then the stability of active ingredients is improved, but the manufacturing complexity and cost increase
Solution Approach 1:
By merging HCl and H3PO4 into the formulation, the patent achieves the stability previously only attainable with FEP coated cans, but using simpler uncoated aluminum canisters, thereby improving ease of manufacture.
Solution Approach 2:
The invention replaces the expensive and complex FEP coated canister with a cheaper, simpler uncoated aluminum canister. The formulation itself becomes the stabilizing element rather than relying on expensive packaging materials.
3Ease of manufacture
If the formulation is stored in aluminum canisters without special coating, then the manufacturing is simplified, but the stability of LABA agents deteriorates over time
Solution Approach 1:
The mixture of HCl and H3PO4 acts as an intermediary protective system between the LABA agent and the aluminum canister environment. This acid mixture creates a chemical environment that prevents degradation, allowing the use of simple aluminum canisters while maintaining stability.
Solution Approach 2:
The formulation includes pre-added HCl and H3PO4 that proactively prevent degradation reactions before they can occur. This preliminary protective action ensures LABA agent stability throughout the product lifetime without requiring special canister coatings.
4Stability of the object's composition
If the concentration of HCl is increased to improve stability, then the stability profile is improved, but the degradation of active ingredients increases due to excessive acid concentration
Solution Approach 1:
The patent changes the parameter composition from a single acid system to a dual acid system (HCl and H3PO4). This parameter change allows for optimized acid concentrations that provide stability without the harmful effects of excessive single-acid concentration, as the two acids work synergistically at lower individual concentrations.
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 combination of HCl and H3PO4 significantly increases the stability of active ingredients, ensuring a consistent delivery and extended shelf life, while allowing the use of commercially available aluminum canisters, thus simplifying manufacturing and maintaining optimal chemical conditions.
Implementation Method 1
the inclusion of a mixture of inorganic acids in a formulation comprising a LABA agent, optionally in combination with a LAMA agent and/or a corticosteroids substantially avoids the degradation of said active ingredients, thus maintaining the formulation stable over an extended period
Implementation Method 2
pMDI devices may use a propellant to expel droplets containing the pharmaceutical products to the respiratory tract as an aerosol
Data Source
AI summary
The present invention generally relates to pharmaceutical composition comprising a LABA agent, optionally in combination with other active ingredients, a mixture of at least two inorganic acids, a propellant and a co-solvent. The invention also provides a pharmaceutical composition for the treatment of respiratory diseases, such as asthma and COPD.