Ipratropium Bromide Inhaler Composition for Stable Dosing
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Solution Overview
Problem
Metered dose inhalers face challenges with chemical stability of active ingredients, particularly ipratropium bromide, due to dehydration and degradation issues, and inconsistencies in dose delivery due to medicament accumulation and deposition in the actuator.
Innovation Solution
A metered dose inhaler device with a stable inhalable composition of ipratropium bromide, using a canister with a metering valve and an actuator, optimized with specific sump volume, nozzle bore diameter, and jet length, along with a cosolvent and stabilizer, to maintain composition stability and consistent dose delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If water is minimized or excluded from the aerosol composition to enhance chemical stability, then chemical stability of ipratropium bromide is improved, but the active ingredient may dehydrate and degrade when water level is too low
Solution Approach 1:
The patent optimizes the water content parameter within a specific range (0.1-5% w/w) to balance two opposing requirements: enough water to maintain the hydrate form of ipratropium bromide and prevent degradation, but limited water to minimize chemical degradation reactions. This parameter optimization resolves the contradiction by finding the precise window where both stability aspects are satisfied.
Solution Approach 2:
The patent introduces a cosolvent system (alcohol or ether) that creates a localized microenvironment around the ipratropium bromide hydrate. This local quality modification allows the active ingredient to maintain its hydrated state without requiring bulk water, thereby preventing dehydration while limiting overall water content to reduce chemical degradation.
2Productivity
If solution composition is used to provide smaller MMAD and deliver to alveolar regions, then delivery efficiency is improved, but chemical stability of active ingredients deteriorates
Solution Approach 1:
The patent creates a composite aerosol composition containing ipratropium bromide hydrate, HFA propellant, and cosolvent (alcohol or ether). This composite formulation allows the active ingredient to maintain its stable hydrate form while being delivered as an aerosol solution with fine particle characteristics, thereby achieving both delivery efficiency and chemical stability.
Solution Approach 2:
The cosolvent (alcohol or ether) acts as an intermediary substance that facilitates the formation and stabilization of the ipratropium bromide hydrate in the aerosol solution. This intermediary enables the active ingredient to maintain its stable hydrated form while being dispersed in the propellant-based aerosol, resolving the contradiction between solution delivery and chemical stability.
3Reliability
If medicament accumulation and deposition in the actuator occurs, then dose consistency deteriorates, but this can be reduced by optimizing actuator geometry
Solution Approach 1:
The patent optimizes specific geometric parameters of the actuator including sump volume (10-50 μL), nozzle bore diameter (0.2-0.6 mm), and jet length (0.25-1.0 mm). These parameter optimizations control the aerosol flow and medicament deposition patterns, reducing accumulation in the actuator and improving dose consistency without requiring complex design 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 device ensures chemical stability of ipratropium bromide, reduces dose inconsistencies, and provides efficient delivery to the respiratory tract with a mean median aerodynamic diameter of 2-4 μm and fine particle fraction of 30-60%, ensuring effective treatment of respiratory disorders.
Implementation Method 1
the administration of aerosol solution compositions by a MDI device is dependent on the propellant force of the propulsion system used to produce them
Implementation Method 2
the composition for treating respiratory disorders are administered in the form of aerosols dispensed as solutions or suspensions of drugs mixed with liquefied gases known as propellants
Data Source
AI summary
The present invention relates to a metered dose inhaler device comprising a stable inhalable composition of ipratropium bromide, contained in a canister fitted with a metering valve, an actuator and a dose indicator. The present invention also relates to a process for preparing such a pharmaceutical composition and its use in the treatment of respiratory disorders such as for the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema in a subject in need thereof (e.g., a human).