Inhalation Powder Stability via Water Activity Control
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Solution Overview
Problem
Existing pharmaceutical compositions for inhalation that combine tiotropium salts and salmeterol with lactose lack stability, leading to changes in chemical and physical properties over time, affecting their efficacy and consistency.
Innovation Solution
The development of inhalation powders with a specific aw value between 0.1 and 0.4, achieved through controlled moisture conditioning and packaging, ensures the stability of tiotropium and salmeterol salts with lactose, maintaining a high fine particle fraction and consistency during storage and inhalation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If conventional desiccants are used to remove moisture from packaging, then moisture control is improved, but uncontrollable residual moisture occurs and stability deteriorates
Solution Approach 1:
The invention changes the water activity parameter from uncontrolled residual moisture to a specific controlled range (aw 0.1-0.4). This is achieved by adjusting the moisture content of the inhalation powder itself rather than relying solely on external desiccants, thereby achieving both moisture control and stability
Solution Approach 2:
The inhalation powder acts as an intermediary between the environment and the active ingredients. By controlling the water activity of the powder matrix, it mediates the moisture environment to prevent both excessive drying and moisture accumulation, thereby protecting the chemical and physical stability of the formulation
2Object-affected harmful factors
If excess desiccant is added to achieve reliable drying, then moisture removal is improved, but the system complexity and loss of substance increase
Solution Approach 1:
The inhalation powder serves itself by having its water activity controlled within the specific range. This self-regulating approach eliminates the need for excessive external desiccants, as the powder matrix itself maintains the appropriate moisture environment through its controlled water activity
Solution Approach 2:
The invention shifts from using large amounts of desiccant to controlling the water activity parameter of the powder itself. This parameter change achieves effective moisture control with minimal additional materials, reducing both system complexity and substance loss
3Duration of action of stationary object
If inhalation powders are stored for long periods, then durability is improved, but chemical and physical stability deteriorates
Solution Approach 1:
The invention maintains stability during long-term storage by controlling the water activity parameter within the specific range of aw 0.1-0.4. This parameter control prevents both dehydration and moisture accumulation that would otherwise occur during extended storage periods
Solution Approach 2:
The water activity is controlled in advance during manufacturing to establish a stable moisture environment. This preliminary control prevents subsequent chemical and physical changes during storage, ensuring stability throughout the product lifecycle
4Ease of operation
If micronization is used to produce respirable particles, then inhalability is improved, but the fine particle fraction may be lost during processing
Solution Approach 1:
The invention controls the water activity parameter to maintain fine particle integrity during micronization and storage. This parameter control prevents aggregation and loss of the fine particle fraction while preserving the respirable particle characteristics necessary for inhalability
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 approach results in stable inhalation powders with a high fine particle dose and consistent delivery, independent of flow rates, maintaining stability and efficacy over 18 months under controlled conditions.
Implementation Method 1
The inhalation powders according to the invention are characterized in that they have an aw value between 0.1 and 0.4... the inhalation powder is exposed to moisture so that an aw value at 25°C between 0.1 and 0.4 is in equilibrium over the inhalation powder
Data Source
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AI summary
The invention relates to stable preparations in powder form for inhalation comprising a tiotropium salt and salmeterol xinafoate, process for the production thereof, and the use thereof for manufacturing a medicament for the treatment of respiratory disorders, especially for the treatment of COPD (chronic obstructive pulmonary disease) and asthma.