Microparticle Encapsulation of Sub-Micron APIs for Bioavailability
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Solution Overview
Problem
Existing pharmaceutical processing methods face challenges in producing sub-micron particles of low bioavailability drugs without thermal degradation, large particle size distribution, and difficulty in handling and scaling up, while conventional spray drying techniques can degrade thermally labile drugs and produce broad particle distributions.
Innovation Solution
A method using a high-throughput installation at room or near room temperature that combines high voltage and nebulizing to encapsulate sub-micron active pharmaceutical ingredients (APIs) within microparticles, ensuring controlled particle size and distribution, using a facility with an injection unit, drying unit, and collection unit to produce free-flowing microparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If spray drying technique is used to prepare pharmaceutical powders, then dehydration and encapsulation can be achieved, but thermally labile drugs are degraded and particle size distribution becomes broad
Solution Approach 1:
The patent changes the temperature parameter from high temperature (conventional spray drying) to room temperature or near room temperature, preventing thermal degradation of labile drugs while maintaining encapsulation capability. This parameter change resolves the contradiction between manufacturing feasibility and particle size control.
Solution Approach 2:
The patent replaces the thermal field (heat-based spray drying) with a mechanical field (high voltage nebulization), achieving dehydration and encapsulation without thermal stress. This substitution eliminates thermal degradation while maintaining particle size control.
2Manufacturing precision
If high voltage and nebulizing are combined at room temperature, then sub-micron particles with narrow size distribution are produced, but the process complexity increases
Solution Approach 1:
The patent merges high voltage nebulization with room temperature drying in a single integrated process step, eliminating the need for separate heating and drying stages. This combination achieves precise particle size control while managing process complexity through integration.
Solution Approach 2:
The high voltage nebulization system performs multiple functions simultaneously: atomization, dehydration, and encapsulation formation. This multi-functionality reduces the number of separate process steps needed, managing complexity while achieving precise particle size control.
3Reliability
If sub-micron particles are produced by conventional techniques, then solubility and bioavailability are improved, but handling and scaling up become difficult
Solution Approach 1:
The patent nests sub-micron particles within microparticles, creating a hierarchical structure where small high-value particles are contained within larger easier-to-handle carriers. This nesting approach maintains the solubility and bioavailability benefits of sub-micron particles while improving handling and scaling capabilities.
Solution Approach 2:
The patent segments the drug material into sub-micron particles dispersed within a matrix of microparticles. This segmentation allows the drug to maintain its high surface area-to-volume ratio for improved solubility while the microparticle matrix provides bulk handling properties for industrial scaling.
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 enables the production of pharmaceutical formulations with improved solubility and bioavailability by encapsulating APIs in sub-micron form within microparticles, allowing for easier handling and processing into conventional pharmaceutical forms, reducing dosage requirements and adverse effects.
Implementation Method 1
a high throughput installation that works at room or near room temperature and that combines high voltage and nebulizing
Implementation Method 2
a high throughput installation that works at room or near room temperature and that combines high voltage and nebulizing
Implementation Method 3
U. Selvaraj and G.L. Messing prepared crystallites of naproxen of 35 nm inside a matrix of ethyl cellulose, with a microparticle size of 400 μm by spray drying
Data Source
AI summary
The present invention relates to a pharmaceutical formulation comprising at least one active pharmaceutical ingredient (API) having low aqueous solubility or a pharmaceutically acceptable salt thereof in the form of particles of a size between 1 and 800 nm, wherein said particles are encapsulated within a large microparticle of a size between 1 and 100 μm formed by a matrix comprising at least an excipient. Therefore, the API is entrapped or encapsulated in the microparticles of excipients. This pharmaceutical formulation contains the pharmaceutical active ingredient having improved solubility and subsequently supra-bioavailability.