MDI Particle Size Control via Bulking Agents
Solution Overview
Problem
Metered Dose Inhalers (MDIs) face challenges in controlling the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of aerosol particles, leading to inefficient drug delivery to the respiratory tract, with a significant portion often being swallowed instead of reaching the lungs, and complicating the co-deposition of drug combinations.
Innovation Solution
Incorporating a non-drug particulate bulking agent, such as lactose, into the solution formulation to modify the MMAD and GSD, and reducing the mass median diameter of suspended drug particles to less than 1.7 microns, especially to 1.4 microns or less, to enhance co-deposition of drugs in MDIs, allowing for improved delivery to specific airway regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional micronized drug particles (2-5 microns MMD) are used in suspension, then the formulation is easier to manufacture, but the co-deposition of drugs to the same respiratory tract locations is insufficient
Solution Approach 1:
The patent applies parameter changes by reducing the mass median diameter (MMD) of suspended drug particles from conventional 2-5 microns to less than 1.7 microns (preferably 1.4 microns or less, most preferably 1.0 micron or less). This significant reduction in particle size parameter enables both drugs in the combination formulation to be delivered to the same respiratory tract locations, achieving effective co-deposition while maintaining manufacturability through established micronization techniques.
2Ease of operation
If dissolved drug formulations are used, then the drug delivery is simpler, but the particle size distribution (MMAD and GSD) cannot be controlled to achieve desired airway deposition
Solution Approach 1:
The patent introduces a non-drug particulate bulking agent (such as lactose, sucrose, glucose, mannitol, or starch) as an intermediary substance in the dissolved drug formulation. This bulking agent serves as a mediator that modifies the particle size distribution (MMAD and GSD) of the aerosol, enabling controlled delivery to specific airway regions while maintaining the simplicity of dissolved drug formulations. The bulking agent acts as a carrier that does not interfere with the therapeutic action of the dissolved drug.
3Ease of operation
If most of the drug is delivered to the mouth, then the formulation is easier to administer, but the therapeutic effectiveness is reduced because the drug does not reach the lung
Solution Approach 1:
The patent applies parameter changes by precisely controlling the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the aerosol particles through the use of particulate bulking agents. By optimizing these particle size parameters, the formulation achieves enhanced deposition in the respiratory tract (lungs) while reducing oral deposition, thereby improving therapeutic effectiveness without compromising administration ease.
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 approach significantly modifies the particle size distribution and co-deposition characteristics of MDI aerosols, ensuring more effective delivery of drugs to the desired locations within the respiratory tract, enhancing therapeutic outcomes by improving the co-deposition of drug combinations.
Implementation Method 1
MDIs use high-pressure liquefied propellants to atomize the formulation into small droplets capable of delivering drug into the regions of the respiratory tract
Implementation Method 2
MDIs use high-pressure liquefied propellants to atomize the formulation
Implementation Method 3
using extra-fine suspended drug particles of less than 1.7 micron MMD results in enhanced co-deposition of the drugs to the same parts of the respiratory tract
Data Source
Figure 1
AI summary
Provided herein are formulations, methods, and metered dose inhaler drug delivery devices. The formulations and methods may provide for controlled particle size delivery in metered dose inhaler drug delivery devices. Further provided are metered dose inhaler drug delivery devices that may themselves deliver controlled sized particles to the airways.