Porous Silicon Carrier Solid Dispersion for Poorly Soluble Drug Bioavailability

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current solid dispersions using porous carriers for poorly soluble active ingredients, such as fibrate compounds, face challenges in achieving improved solubility and bioavailability due to issues like large particle size, reduced dispersibility, and complex production processes, especially when subjected to compression molding.

Innovation Solution

A solid dispersion utilizing a specific porous silicon-containing carrier with characteristics like spherical silica, controlled pore size, and surface treatment to support the active ingredient, allowing for improved solubility and bioavailability without the need for supercritical fluids or complex processing steps.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional porous carriers (e.g., silic anhydride) are used to improve solubility of poorly soluble active ingredients, then solubility is enhanced, but the preparation size becomes large and dispersibility deteriorates due to strong bonding during compression molding

Engineering Contradiction:
ImprovesolubilityVSAvoidpreparation size
Core Design Contradiction:
ReliabilityVSVolume of moving object

Solution Approach 1:

The patent employs porous silicon-containing carriers with specifically controlled pore structures (mean pore size 3-20 nm, pore volume 0.3-2.0 mL/g) to achieve high solubility enhancement while maintaining compact preparation size. The porous structure provides large surface area for drug loading without increasing bulk volume excessively.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent modifies key parameters of the porous carrier including particle size (3-15 μm), pore size (15-20 nm), and surface treatment (heating loss ≤2.5% at 950°C) to optimize both solubility enhancement and compression molding properties, resolving the contradiction between solubility improvement and preparation size control.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If porous carriers with high surface area are used to enhance solubility, then solubility improves, but compression molding causes strong bonding that reduces dispersibility and dissolution rate

Engineering Contradiction:
ImprovesolubilityVSAvoiddispersibility
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent optimizes the heating loss parameter (≤2.5% at 950°C for 2 hours) to control the degree of surface treatment and sintering, thereby balancing solubility enhancement with maintenance of dispersibility after compression molding. This parameter control prevents excessive bonding while preserving porous structure.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite porous silicon-containing carriers that combine silica with other materials (such as metal oxides or organic-inorganic hybrids) to achieve both high solubility enhancement and good compressibility without losing dispersibility, resolving the contradiction between solubility and ease of operation.

Inventive Principle:
Principle #40Composite materials

3Reliability

If fine particle size of active ingredient is used to improve solubility, then solubility enhances, but handleability in production process deteriorates

Engineering Contradiction:
ImprovesolubilityVSAvoidhandleability
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses porous carriers with controlled pore sizes (15-20 nm) to adsorb and stabilize fine active ingredient particles, preventing their aggregation and improving handleability during production while maintaining the solubility benefits of fine particle size.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The porous carrier acts as an intermediary that holds the fine active ingredient particles, improving their handleability during processing. The carrier provides a matrix that prevents fine particles from becoming unmanageable while preserving their high surface area for solubility enhancement.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Reliability

If supercritical fluid treatment or complex processing steps are used to improve solubility, then solubility enhances, but production process complexity increases

Engineering Contradiction:
ImprovesolubilityVSAvoidproduction process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The porous silicon-containing carriers are prepared in advance with controlled pore structures and surface properties, enabling them to enhance solubility through simple mixing and compression without requiring supercritical fluid treatment or complex processing steps during pharmaceutical manufacturing.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The porous carriers are pre-treated with controlled heating (to achieve ≤2.5% heating loss) and pore structure optimization before use, so that they can directly enhance solubility through simple formulation processes without requiring complex supercritical fluid treatment or additional processing steps during production.

Inventive Principle:
Principle #10Preliminary action

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 solution significantly enhances the solubility and bioavailability of the active ingredient, enabling a compact pharmaceutical form with improved patient compliance and efficient production, even when subjected to compression molding.

Implementation Method 1

a solid dispersion comprising an active ingredient hardly soluble in water and a powdery porous carrier impregnated with and supporting the active ingredient

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

the porous carrier comprises at least a first porous silicon-containing carrier comprising a spherical porous silica with a BET specific surface area of 400 to 600 m2/g

Methodology Applied
Scientific EffectPorosity: Porosity

Data Source

PatentEP2251038B1Solid dispersion, pharmaceutical compositions containing the same, and processes for the production of both
Publication Date: 2017.05.10 ASKA PHARMACEUTICAL CO LTD
  • EP2251038B1 patent drawingFigure 1~2
  • EP2251038B1 patent drawingFigure 3~4
  • EP2251038B1 patent drawingFigure 5~6

AI summary

A powdery porous carrier comprising a porous silicon-containing carrier is impregnated with a solution containing an organic solvent and an active ingredient hardly soluble in water, and the organic solvent is removed to give a solid dispersion having the active ingredient supported to the porous carrier without a treatment with a supercritical fluid. The porous silicon-containing carrier has a heating loss of not more than 4% by weight at a temperature of 950°C for 2 hours (e.g., a spherical silicon-containing carrier such as a spherical porous silica). The porous silicon-containing carrier may be a spherical silica having a mean pore size of 10 to 40 nm and an oil absorption of 175 to 500 ml/100g. A pharmaceutical composition (e.g., tablets, granules, or capsules) may be prepared from the solid dispersion and a pharmaceutically acceptable carrier. This invention provides a solid dispersion and a pharmaceutical composition (or a pharmaceutical preparation) which allows improvement in a solubility and a bioavailability of an active ingredient hardly soluble in water (e.g., a fibrate compound).