Coated Crystalline DPI Composition for High-Load Aerosolization
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Solution Overview
Problem
Existing dry powder inhaler (DPI) formulations face challenges in delivering high API loads due to strong cohesive and adhesive forces between micronized drug substance particles, leading to poor aerosolization performance and stability issues, particularly in high dosage formulations.
Innovation Solution
A process involving micronization of crystalline API followed by suspension in an antisolvent with dissolved FCA, then spray-drying to coat the API with FCA, ensuring controlled particle size distribution and maintaining crystallinity, thereby improving aerosolization performance and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If micronized API particles are used to achieve respirable size range, then particle size is reduced for inhalation, but inter-particulate cohesive forces increase leading to poor aerosolization performance
Solution Approach 1:
A force control agent (FCA) is introduced as an intermediary substance that coats the surface of micronized API particles. The FCA modifies inter-particulate forces by reducing cohesive forces between particles, thereby improving aerosolization performance while maintaining the required respirable particle size range for inhalation delivery
2Quantity of substance
If high API load is formulated to achieve high dosage, then drug loading is increased, but cohesive forces between particles increase leading to stability issues and poor aerosolization
Solution Approach 1:
The force control agent is applied locally on the surface of each API particle through coating, creating a localized modification of inter-particulate forces at the particle surface. This local quality change allows high API loading in the bulk formulation while maintaining reduced cohesive forces at particle interfaces, thereby preserving aerosolization performance even at high dosages
3Ease of manufacture
If impact methods such as mechanofusion are used to apply FCA, then FCA coating is achieved, but uncontrolled particle modification and chemical degradation occur
Solution Approach 1:
The patent employs spray drying technology to control the physical and chemical parameters of the coating process. By controlling parameters such as spray rate, drying temperature, and solvent evaporation rate, the process achieves FCA coating while maintaining precise control over particle size distribution and preventing chemical degradation of the API, unlike high-energy impact methods
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 process results in a pharmaceutical composition with enhanced aerosolization performance and stability, achieving higher fine particle fractions and reduced variability, suitable for high dosage inhalation treatments.
Implementation Method 1
Removal of the antisolvent from the mixture by spray drying, so as to obtain coating of the micronized crystalline API with the dissolved FCA
Data Source
AI summary
The present invention describes a dry powder inhaler pharmaceutical composition comprising one or more active pharmaceutical ingredients (API) coated with one or more force control agents (FCA) with optimized aerodynamic performance by micronizing crystalline API particles to the respirable range and coating the particles with a force control agent. The present invention also id pharmaceutical composition, and its use in medicine.