Cannabigerol Proline Cocrystals for Pharmaceutical Stability

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Solution Overview

Problem

Cannabigerol's low melting point and polymorphic nature make it unsuitable for solid oral dosage forms, as it is prone to degradation and polymorphic changes during drug product manufacture, posing challenges for stability and consistency in pharmaceutical formulations.

Innovation Solution

The development of cannabigerol proline cocrystals, specifically 1:2 cannabigerol L-proline, D-proline, and D,L-proline cocrystals, which offer a stable solid form with a higher melting point and reduced polymorphic interconversion, suitable for pharmaceutical compositions and formulations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If cannabigerol is used in solid oral dosage forms, then it can be administered orally, but it undergoes polymorphic changes and degradation during manufacturing due to its low melting point

Engineering Contradiction:

Improveoral dosage form formulationVSAvoidpolymorphic stability

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter of cannabigerol by forming a cocrystal with proline, which raises the melting point from below 50°C to above 150°C. This parameter change enables the substance to withstand manufacturing temperatures without polymorphic transformation or degradation, while maintaining oral dosage form capability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite crystalline structure by combining cannabigerol with proline in a 1:2 molar ratio to form a new cocrystal phase. This composite material exhibits enhanced thermal stability and polymorphic consistency compared to pure cannabigerol, resolving the contradiction between manufacturability and compositional stability.

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If cannabigerol is used in pharmaceutical formulations, then it can treat various conditions, but it lacks consistent stability and bioavailability

Engineering Contradiction:

Improvetherapeutic applicationsVSAvoidformulation stability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent modifies the thermal and crystalline parameters of cannabigerol through cocrystal formation, establishing a consistent melting point above 150°C and eliminating polymorphic variability. This parameter standardization ensures reliable and consistent bioavailability across different formulation types and manufacturing batches, thereby improving formulation reliability while preserving therapeutic versatility.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If cannabigerol is processed at elevated temperatures, then manufacturing can proceed, but the low melting point causes degradation and polymorphic changes

Engineering Contradiction:

Improvemanufacturing efficiencyVSAvoiddegradation and polymorphic changes

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent fundamentally changes the thermal parameter of cannabigerol by raising the melting point through cocrystal formation. This enables the substance to be processed at elevated temperatures (above its new melting point) without undergoing degradation or polymorphic changes, thus eliminating harmful factors while maintaining manufacturing efficiency.

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 cannabigerol proline cocrystals provide a stable and consistent form of cannabigerol, maintaining its crystalline structure during processing and storage, ensuring improved stability and bioavailability, thus addressing the limitations of cannabigerol's free form in pharmaceutical development.

Implementation Method 1

maintaining its crystalline structure during processing and storage

Methodology Applied

Scientific EffectCrystalline structure stability:

Implementation Method 2

reduced polymorphic interconversion

Methodology Applied

Scientific EffectPolymorphic stability: Metastability

Implementation Method 3

higher melting point

Methodology Applied

Scientific EffectMelting point elevation: Melting

Data Source

PatentUS20220332682A1Caanabigerol proline cocrystals

Publication Date: 2022.10.20 MANOIRA CORP

AI summary

Cannabigerol proline cocrystals are disclosed, specifically a 1:2 cannabigerol L-proline cocrystal, a 1:2 cannabigerol D-proline cocrystal and a 1:2 cannabigerol D, L-proline cocrystal and their preparation. Also disclosed are pharmaceutical compositions containing a cannabigerol proline cocrystal and a pharmaceutically acceptable excipient as well as methods and uses of a cannabigerol proline cocrystal or pharmaceutical composition to treat a disease, disorder or condition by administering to a patient in need thereof a therapeutically effective amount of a cannabigerol proline cocrystal or a pharmaceutical composition containing a cannabigerol proline cocrystal. Also disclosed are processes for the preparation of crystalline cannabigerol, Forms I, II and III.