Delamanid Particle Stabilization via Surface Mediator
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Solution Overview
Problem
Current delamanid formulations face challenges in solubility and drug absorption due to high costs and environmental burdens associated with organic solvent treatment, and the difficulty in milling delamanid into fine particles without aggregation.
Innovation Solution
A composition comprising delamanid particles and a specific surface stabilizer, such as hydroxypropyl cellulose and sucrose fatty acid ester, is used to enhance milling efficiency and prevent particle aggregation, improving solubility and absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If delamanid is milled in water to increase specific surface area, then particle size is reduced, but particles aggregate due to intermolecular force, capillary force, and electrostatic force
Solution Approach 1:
A surface stabilizer is introduced as an intermediary substance between water and delamanid particles. The surface stabilizer adsorbs onto the particle surface, providing steric or electrostatic repulsion that prevents aggregation while allowing efficient milling to occur in the aqueous medium.
Solution Approach 2:
The patent changes the surface properties of delamanid particles by introducing a surface stabilizer, which modifies the interfacial parameters between the hydrophobic drug and aqueous medium. This parameter change enables stable dispersion of fine particles without aggregation.
2Ease of manufacture
If delamanid is dissolved together with polymer in organic solvent followed by spray drying, then solubility is improved and drug absorption is enhanced, but treatment cost increases and environmental burden arises due to solvent recovery requirements
Solution Approach 1:
The patent changes the solvent system from organic solvent to water by introducing a surface stabilizer. This parameter change maintains the ability to form fine particles with good solubility and absorption while eliminating the need for expensive organic solvent recovery processes.
Solution Approach 2:
The patent replaces expensive organic solvents that require recovery with water, which is inexpensive and environmentally benign. The surface stabilizer enables this substitution by preventing particle aggregation in the aqueous system.
3Volume of moving object
If delamanid is milled to produce submicron particles, then specific surface area increases, but milling efficiency decreases due to extreme hydrophobicity making it difficult to mill in water
Solution Approach 1:
The surface stabilizer acts as a mediator between the hydrophobic delamanid and the aqueous milling medium. It reduces interfacial tension and prevents particle aggregation during milling, enabling efficient size reduction to submicron particles with high specific surface area.
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 composition effectively suppresses secondary particle formation, enhances dissolution rates, and allows for efficient milling of delamanid, reducing environmental impact and improving pharmaceutical formulations.
Implementation Method 1
the solubility of delamanid is improved and drug absorption is enhanced by dissolving delamanid together with a polymer in an organic solvent
Implementation Method 2
the submicron particles easily aggregated due to the aggregation force (e.g., intermolecular force, capillary force, and electrostatic force) acting after milling
Implementation Method 3
A first attempt was made to increase the specific surface area by milling delamanid in water until it became fine particles (submicron particles)
Implementation Method 4
the solubility of delamanid is improved and drug absorption is enhanced
Data Source
AI summary
Provided is a composition comprising delamanid particles for which the formation of secondary particles is suppressed. Specifically, provided is a composition comprising (A) delamanid particles and (B) a surface stabilizer.