Amorphous API–Mesoporous Magnesium Carbonate for Improved Solubility

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Solution Overview

Problem

Poorly soluble active pharmaceutical ingredients (APIs) face challenges with insufficient solubility and stability in aqueous media, leading to poor bioavailability and variability in drug exposure, and existing formulation techniques fail to provide long-term stability and patient-friendly dosage forms.

Innovation Solution

A solid, substantially amorphous active pharmaceutical ingredient is developed, comprising at least 20% API admixed with anhydrous and amorphous mesoporous magnesium carbonate (MMC) with specific pore sizes, surface areas, and particle distributions, which stabilizes the API during storage and allows high loading without increasing tablet or capsule size.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If amorphous forms of drug substances are used to improve solubility and dissolution rate, then solubility is improved, but storage stability deteriorates

Engineering Contradiction:

ImprovesolubilityVSAvoidstorage stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent employs mesoporous magnesium carbonate as a carrier material with controlled pore sizes (2-10 nm) and surface area (250-600 m2/g). The porous structure provides high surface area for API loading while maintaining amorphous form through confinement effects in the pores, resolving the contradiction between solubility enhancement and storage stability

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The invention creates a composite system combining amorphous API with mesoporous magnesium carbonate. This composite maintains the API in amorphous form through physical confinement in the porous structure, achieving both improved solubility/dissolution and enhanced storage stability through the synergistic interaction between components

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If high API load is used to increase bioavailability, then therapeutic efficacy is improved, but tablet or capsule size increases

Engineering Contradiction:

ImproveAPI loadVSAvoidtablet or capsule size

Core Design Contradiction:

Quantity of substanceVSVolume of moving object

Solution Approach 1:

The patent loads API molecules into the nested pore structure of mesoporous magnesium carbonate particles. This nesting approach allows high API loading (up to 60% w/w) within the confined space of individual particles, enabling high therapeutic content without increasing external tablet or capsule size

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The mesoporous structure with optimized pore size (2-10 nm) and surface area (250-600 m2/g) provides high internal volume for API accommodation. This porous architecture enables high API load while maintaining compact particle size, thus resolving the contradiction between API load and dosage form size

Inventive Principle:

Principle #31Porous materials

3Quantity of substance

If existing formulation techniques are used to improve solubility, then aqueous solubility is improved, but long term stability deteriorates

Engineering Contradiction:

Improveaqueous solubilityVSAvoidlong term stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent uses mesoporous magnesium carbonate with specifically controlled pore sizes (2-10 nm) that confine the API in a way that maintains amorphous form during storage. This physical confinement in controlled pores prevents crystallization while preserving solubility enhancement, achieving both improved aqueous solubility and long term stability

Inventive Principle:

Principle #31Porous materials

Solution Approach 2:

The invention optimizes specific parameters of the mesoporous carrier including pore size (2-10 nm), surface area (250-600 m2/g), and particle size distribution (d10: 70-430 μm). These parameter changes create optimal conditions for maintaining API in amorphous form while enhancing solubility, resolving the stability issue with existing formulations

Inventive Principle:

Principle #35Parameter changes

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 formulation maintains API in an amorphous form, enhancing solubility and stability, ensuring therapeutic efficacy and patient compliance by maintaining amorphous form during storage and allowing high API loads without size increase.

Implementation Method 1

a particulate anhydrous and substantially amorphous mesoporous magnesium carbonate (MMC), wherein said MMC has: (i) pores with an average pore size in the range of 2 nm to 10 nm

Methodology Applied

Scientific EffectPhysical confinement in porous structure: Porosity

Implementation Method 2

amorphous forms of drug substances provide a better solubility and dissolution rate than the corresponding crystal form

Methodology Applied

Scientific EffectAmorphous state solubility enhancement:

Data Source

PatentUS12459829B2Amorphous active pharmaceutical ingredients comprising substantially amorphous mesoporous magnesium carbonate

Publication Date: 2025.11.04 DISRUPTIVE PHARMA AB

AI summary

A solid and substantially amorphous admixture comprising Sorafenib as active pharmaceutical ingredient (API) and a particulate anhydrous and substantially amorphous mesoporous magnesium carbonate (MMC), a method for the manufacture thereof, and an oral pharmaceutical formulation comprising the solid substantially amorphous admixture.