MDI Propellant Suspension via Solubilized Excipient Transfer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional methods for preparing metered dose inhaler (MDI) compositions face challenges in controlling particle size distribution and maintaining the stability of pharmaceutically-active compounds, leading to inconsistent dose delivery and regulatory compliance issues.
Innovation Solution
A method involving the transfer of a solubilized excipient mixture, including a hydrofluoroalkane propellant and a poly(ethylene oxide) polymer, into a vessel containing a pharmaceutically-active compound, under controlled pressure and temperature conditions, to facilitate the formation of a homogeneous pharmaceutical composition suitable for MDIs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods (milling, spray drying, supercritical fluid recrystallization) are used to prepare medicament powders for MDI compositions, then particle size control is achieved, but dissolution of medicament powder in excipients during manufacture occurs, resulting in loss of particle size control
Solution Approach 1:
The medicament powder is pre-coated with a hydrophobic coating material before being mixed with the propellant and excipient. This preliminary coating action prevents dissolution of the medicament powder in the excipient during subsequent manufacturing steps, thereby maintaining particle size control throughout the process.
Solution Approach 2:
A hydrophobic coating material serves as an intermediary layer between the medicament powder and the excipient. This coating layer acts as a barrier that prevents direct contact and dissolution of the medicament in the excipient, while still allowing the propellant to effectively suspend the coated particles.
2Ease of manufacture
If medicament powder is mixed directly with propellant and excipient, then manufacturing process is simplified, but inconsistent dose delivery and regulatory compliance issues occur due to poor suspension and particle size distribution
Solution Approach 1:
The medicament powder is pre-coated with hydrophobic material before mixing with propellant and excipient. This preliminary step ensures proper suspension characteristics and consistent particle size distribution in the final aerosol, leading to reliable dose delivery without complicating the overall manufacturing process.
Solution Approach 2:
The surface properties of the medicament powder are modified by applying a hydrophobic coating, changing its interaction with the excipient and propellant. This parameter change improves suspension stability and particle size distribution, ensuring consistent dose delivery while maintaining manufacturing simplicity.
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
This method enhances the suspension of pharmaceutically-active compounds in the propellant, ensuring consistent particle size distribution and improved stability, thereby meeting regulatory requirements and enhancing the efficiency of aerosol delivery.
Implementation Method 1
a solubilized excipient mixture, including a hydrofluoroalkane propellant and a poly(ethylene oxide) polymer
Implementation Method 2
enhances the suspension of pharmaceutically-active compounds in the propellant, ensuring consistent particle size distribution
Data Source
AI summary
The present disclosure provides a method of preparing a pharmaceutical composition. The method includes transferring a predetermined quantity of an excipient mixture from a second vessel to a first vessel. The excipient mixture transferred from the second vessel includes a liquid-state second quantity of a hydrofluoroalkane propellant and a first solubilized excipient comprising a low-molecular weight poly(ethylene oxide) polymer. The method further includes contacting at least one pharmaceutically-active compound with the excipient mixture under conditions that facilitate forming an intermixture comprising the propellant, the polymer, and the compound. Before transferring the excipient mixture, the first vessel contains a vapor-phase first quantity of the hydrofluoroalkane propellant and an effective amount of the at least one pharmaceutically-active compound.