Ipratropium Bromide MDI Formulation for Stable Fine-Particle Dosing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Metered dose inhalers face challenges with chemical stability of active ingredients in solution compositions, leading to degradation and inconsistencies in dose delivery due to medicament accumulation and deposition, which affects the efficacy and safety of respiratory treatments.

Innovation Solution

A metered dose inhaler device with a stable inhalable composition of ipratropium bromide, utilizing specific actuator parameters such as sump volume, nozzle bore diameter, and jet length, along with a propellant like HFA-134a, and optional cosolvents and stabilizers to maintain composition stability and consistent dose delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If solution compositions are used in MDIs, then smaller mass median aerodynamic diameter is achieved resulting in delivery to the entire lung including alveolar regions, but chemical stability of active ingredients deteriorates leading to degradation

Engineering Contradiction:

Improvemass median aerodynamic diameterVSAvoidchemical stability of active ingredients

Core Design Contradiction:

Volume of moving objectVSStability of the object's composition

Solution Approach 1:

The patent changes the physical-chemical parameters of the composition by using co-solvents (ethanol, isopropanol) in combination with HFA propellants and stabilizers (citric acid, benzoic acid) to maintain chemical stability while achieving fine particle delivery. The specific parameter ranges (e.g., co-solvent 5-50% w/w, stabilizer 0.1-5% w/w) optimize both stability and aerosol performance.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite formulation strategies by combining multiple components: HFA propellants with co-solvents and stabilizers. This composite approach creates a synergistic system where each component contributes to both stability and delivery performance, resolving the contradiction between fine particle generation and chemical stability.

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If water is excluded from the aerosol composition to enhance stability, then chemical stability is improved, but active pharmaceutical ingredients in hydrate form dehydrate and degrade

Engineering Contradiction:

Improvechemical stabilityVSAvoidpharmaceutical acceptability and stability of hydrate forms

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent carefully controls water content within specific ranges (0.1-10% w/w) rather than complete exclusion. This parameter optimization maintains the hydrate form of active ingredients while preventing excessive water uptake that would cause degradation, balancing stability requirements with hydrate preservation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces co-solvents (ethanol, isopropanol) and stabilizers (citric acid, benzoic acid) as intermediary substances that mediate between water and the active ingredient. These intermediaries protect hydrate forms from dehydration while maintaining overall composition stability in the low-water environment.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If medicament accumulation and deposition occur in the actuator, then dose consistency deteriorates and spray orifice blockage occurs, but increasing propellant force to prevent accumulation increases medicament deposition

Engineering Contradiction:

Improvedose consistencyVSAvoidmedicament deposition

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent optimizes propellant composition (HFA-134a with specific co-solvents and stabilizers) and formulation parameters to achieve appropriate spray characteristics. This balanced formulation ensures sufficient propellant force to prevent accumulation while controlling medicament deposition through optimized solubility and spray dynamics.

Inventive Principle:

Principle #35Parameter 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, minimizing degradation and ensuring consistent dose delivery with improved fine particle fraction and median aerodynamic diameter, enhancing treatment efficacy for 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

Methodology Applied

Scientific EffectPropulsion:

Implementation Method 2

Metered dose inhalers (MDIs) are important and well-known devices used to provide effective treatment for many respiratory diseases. In MDIs, the composition for treating respiratory disorders are administered in the form of aerosols

Methodology Applied

Scientific EffectAerosol: Aerosol

Data Source

PatentUS20260077140A1Metered dose inhaler for ipratropium bromide solution

Publication Date: 2026.03.19 GLENMARK PHARMACEUTICALS LTD

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).