R-152a Propellant and Oleic Acid Surfactant for MDI
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Solution Overview
Problem
Current metered dose inhaler (MDI) propellants, such as R-134a and R-227ea, have high global warming potentials, are poorly suited for dissolving pharmaceutical actives, leading to nozzle blockage and irritancy issues, and require polar excipients like ethanol, which can cause large droplet sizes and throat irritation.
Innovation Solution
A pharmaceutical composition using 1,1-difluoroethane (R-152a) as the propellant and oleic acid as the surfactant, eliminating the need for polar excipients and enhancing the stability and delivery of salbutamol sulphate without ethanol, forming a stable suspension for effective inhalation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If R-134a or R-227ea is used as propellant, then global warming potential is reduced compared to CFCs, but the propellant is poorly suited for dissolving pharmaceutical actives leading to nozzle blockage
Solution Approach 1:
A surfactant is introduced as an intermediary substance between the propellant (R-134a or R-227ea) and the pharmaceutical active (salbutamol sulphate). The surfactant acts as a mediator that improves the solubility and compatibility of the drug in the propellant, preventing nozzle blockage while maintaining the environmentally friendly propellant choice.
Solution Approach 2:
The invention creates a composite formulation combining the propellant (R-134a or R-227ea), surfactant, and pharmaceutical active (salbutamol sulphate) in specific proportions. This composite material approach allows the components to work synergistically, with the surfactant enhancing the overall compatibility and preventing the harmful effect of nozzle blockage.
2Stability of the object's composition
If polar excipients like ethanol are added to improve dissolution, then solubility of pharmaceutical actives is enhanced, but droplet size increases and throat irritation occurs
Solution Approach 1:
The surfactant serves as an intermediary that improves the solubility of the pharmaceutical active without requiring polar excipients like ethanol. By acting as a compatibility enhancer, the surfactant allows the drug to dissolve or disperse effectively in the non-polar propellant, avoiding the need for ethanol and thus preventing throat irritation and large droplet formation.
Solution Approach 2:
The invention changes the chemical parameters of the formulation by replacing polar excipients (ethanol) with a surfactant system. This parameter change maintains or improves solubility while eliminating the harmful effects associated with polar excipients, such as throat irritation and excessive droplet size.
3Object-affected harmful factors
If R-152a is used as propellant, then environmental impact is minimized and solubility of salbutamol sulphate is improved, but the propellant requires specific surfactant compatibility
Solution Approach 1:
The invention optimizes the surfactant concentration and type parameters to achieve compatibility with R-152a propellant. By carefully adjusting these parameters, the formulation achieves effective drug solubility and stability while maintaining the environmental benefits of R-152a. The specific surfactant:propellant ratio is optimized to ensure compatibility without excessive complexity.
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 R-152a/oleic acid combination allows for efficient, stable, and irritancy-reduced delivery of salbutamol sulphate as a fine aerosol, improving lung penetration and reducing throat deposition, while minimizing environmental impact.
Implementation Method 1
delivering the salbutamol sulphate from a pressurised aerosol container using a metered dose inhaler (MDI)
Implementation Method 2
deliver the drug as an atomised formulation even at low ambient temperatures
Implementation Method 3
a surfactant component comprising oleic acid
Implementation Method 4
forming a stable suspension for effective inhalation
Data Source
AI summary
A pharmaceutical composition is described that is suitable for delivery from a pressurised container. The composition is free of polar excipients and comprises: (a) a propellant component that consists essentially of 1,1-difluoroethane (R-152a); (b) a surfactant component that comprises oleic acid; and (c) a drug component that consists of salbutamol sulphate. The pharmaceutical composition can be delivered using a metered dose inhaler (MDI).