Algae-Derived Cellulose Amorphous Drug Stabilization

Solution Overview

Problem

Current pharmaceutical formulations of NSAIDs with low solubility, particularly Type 2 and 4 BCS drugs, face challenges in rapid absorption and bioavailability, leading to high doses and increased side effects due to poor solubility and bioavailability, which is crucial for conditions like migraine and dysmenorrhea where quick relief is necessary.

Innovation Solution

A pharmaceutical composition comprising cellulose derived from algae, chemically modified through surface limited reactions with primary and secondary alcohols, is used to enhance the bioavailability and stability of Type 2 and 4 BCS active ingredients, ensuring at least 90% of the active pharmaceutical ingredient is in an amorphous form for rapid release and increased physical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional pharmaceutical formulations of Type 2 and 4 BCS drugs are used, then the drugs can be administered orally, but the solubility and bioavailability are poor leading to high doses and side effects

Engineering Contradiction:

ImprovebioavailabilityVSAvoiddose

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the physical state parameter of the drug from crystalline to amorphous form, and modifies the cellulose structure through chemical derivation. These parameter changes enhance solubility and bioavailability, allowing lower doses to achieve therapeutic effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system combining amorphous drug with chemically modified cellulose (where cellulose hydroxyl groups are replaced by alkoxy groups). This composite structure provides both solubility enhancement and structural stability, resolving the contradiction between dose reduction and therapeutic reliability

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If the drug is kept in crystalline form for stability, then storage is easier, but dissolution and absorption are slow

Engineering Contradiction:

Improvephysical stabilityVSAvoiddissolution rate

Core Design Contradiction:

Stability of the object's compositionVSSpeed

Solution Approach 1:

The patent changes the physical state parameter of the drug from crystalline to amorphous form, and modifies the cellulose structure through chemical derivation. These parameter changes enhance solubility and bioavailability, allowing lower doses to achieve therapeutic effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The chemically modified cellulose acts as an intermediary carrier that stabilizes the amorphous drug state. The alkoxy groups on cellulose prevent drug crystallization while providing structural support, enabling the drug to maintain amorphous state for storage stability yet dissolve rapidly when administered

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If high doses are administered to overcome poor solubility, then therapeutic effect is achieved, but side effects increase

Engineering Contradiction:

Improvetherapeutic effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the physical state parameter of the drug from crystalline to amorphous form, and modifies the cellulose structure through chemical derivation. These parameter changes enhance solubility and bioavailability, allowing lower doses to achieve therapeutic effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the typically harmful amorphous state (which has high energy and tends to crystallize) into a beneficial stable form by using chemically modified cellulose as a stabilizing matrix. This allows the drug to maintain amorphous state for enhanced solubility without the usual instability problems, achieving therapeutic effects at lower doses with reduced side effects

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 achieves rapid release and enhanced bioavailability of Type 2 and 4 BCS active ingredients, reducing the need for high doses and minimizing side effects, while maintaining stability for extended periods, thereby providing effective therapeutic benefits with improved pharmacokinetic profiles.

Implementation Method 1

wherein at least about 90% of the active pharmaceutical ingredient is in an amorphous form

Methodology Applied

Scientific EffectAmorphous form stabilization:

Implementation Method 2

enhancing the bioavailability and stability of Type 2 and 4 BCS active ingredients

Methodology Applied

Scientific EffectSolid-state stabilization:

Implementation Method 3

cellulose that has been chemically modified by way of a surface limited reaction involving primary and secondary alcohols

Methodology Applied

Scientific EffectSurface limited reaction:

Implementation Method 4

provide for rapid release of active ingredients, such as Type 2 and 4 BCS drugs

Methodology Applied

Scientific EffectEnhanced bioavailability:

Data Source

PatentEP3413873B1New compositions

Publication Date: 2023.12.27 VELTIO PHARMA AB

Figure 1(a)~1(b)
Figure 1(c)
Figure 2(a)~2(b)

AI summary

There is provided a pharmaceutical composition comprising cellulose obtained from algae, or a derivative of said cellulose, and an active pharmaceutical ingredient (e.g. from Type 2 and 4 BCS class), wherein the active pharmaceutical ingredient is in a predominantly amorphous form. Compositions of the invention find particularly utility as formulations comprising BCS Type 2 and 4 drugs, including NSAIDs or other drugs, that may be employed in the treatment of migraine or dysmenorrhea, as well as formulations comprising other poorly soluble active ingredients where rapid release in vivo is advantageous.