Co-amorphous Drug-Protein Formulation for Solubility and Stability

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Solution Overview

Problem

The pharmaceutical industry faces challenges in achieving stable and bioavailable oral drug formulations for poorly soluble drug substances due to their low aqueous solubility and instability, particularly in amorphous forms which tend to recrystallize during storage.

Innovation Solution

The development of co-amorphous forms combining poorly soluble substances with proteins like whey protein isolate or whey protein hydrolysate, which enhance solubility and stability by forming a homogeneous, one-phase system, utilizing inexpensive proteins and specific enzymatic treatments to optimize interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If amorphous formulations are used to improve solubility and dissolution rate, then aqueous solubility and dissolution rate are increased, but physical stability deteriorates due to re-crystallization during storage

Engineering Contradiction:

Improveaqueous solubilityVSAvoidphysical stability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies composite materials by combining the amorphous drug substance with a stabilizing excipient to form a co-amorphous system. This composite structure prevents re-crystallization while maintaining enhanced solubility, resolving the contradiction between solubility improvement and physical stability.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The stabilizing excipient acts as an intermediary substance that interacts with the amorphous drug substance to prevent its re-crystallization. This mediator maintains the amorphous state during storage while allowing the drug to retain its improved solubility properties.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If crystalline form is used for oral formulation, then manufacturing is simple and cost-effective, but bioavailability deteriorates due to poor solubility and low dissolution rates

Engineering Contradiction:

Improvemanufacturing simplicityVSAvoidbioavailability

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the physical state parameter of the drug substance from crystalline to amorphous form. This parameter change dramatically improves aqueous solubility and dissolution rate, thereby enhancing bioavailability while still allowing for relatively simple manufacturing processes.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If amorphous form is converted from crystalline to improve solubility, then therapeutic efficacy is improved, but manufacturing precision deteriorates due to physical instability and re-crystallization

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidformulation stability

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

By creating a co-amorphous composite system with a stabilizing excipient, the patent maintains the therapeutic benefits of the amorphous form while achieving the formulation stability needed for precise and reliable manufacturing.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The stabilizing excipient provides beforehand cushioning against the tendency of the amorphous drug to re-crystallize. This preventive measure ensures formulation stability is maintained throughout storage, enabling consistent manufacturing quality.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS20240000945A1Co-amorphous form of a substance and a protein

Publication Date: 2024.01.04 UNIVERSITY OF COPENHAGEN

AI summary

The present invention relates to co-amorphous form of a substance and a protein. The present invention also relates to pharmaceutical, cosmetic or veterinary compositions comprising the co-amorphous form as well as to methods for preparing and using the co-amorphous form.