Synthetic Cannabinoid Crystal Forms for Stable Seizure Drug Formulation
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Solution Overview
Problem
Cannabidiol (CBD) is difficult to formulate into pharmaceutical products due to its highly aliphatic nature, leading to poor solubility and bioavailability, and often precipitates in the GI tract, resulting in higher elimination and poorer absorption.
Innovation Solution
Development of crystalline forms of synthetic cannabidiol-like cannabinoid (1′R,2′R)-5′-methyl-4-(1-methyl-1H-pyrazol-4-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, specifically Forms A, B, C, and E, which exhibit improved chemical stability, high melting points, and stability under various conditions, facilitating easier formulation and handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cannabidiol is used in its natural extracted form, then it maintains its pharmacological properties, but it is difficult to solubilise and formulate due to its highly aliphatic nature and high LogP
Solution Approach 1:
The patent changes the physical state parameter of cannabidiol from amorphous/semi-crystalline to crystalline form. This parameter change improves solubility and formulation ease while maintaining the pharmacological properties of CBD.
Solution Approach 2:
The patent creates a composite system by combining crystalline cannabidiol with specific excipients and formulation technologies that enhance solubility. This composite approach allows the highly lipophilic CBD to be effectively formulated for oral administration.
2Reliability
If extracted cannabidiol is used, then it provides the desired therapeutic effects, but it precipitates in the GI tract leading to higher elimination and poorer absorption
Solution Approach 1:
The patent changes the crystalline structure parameter of CBD, which fundamentally alters its dissolution behavior in the GI tract. The crystalline form prevents precipitation and improves absorption, increasing the quantity of substance that reaches systemic circulation.
Solution Approach 2:
The patent introduces formulation intermediaries such as solubilizing excipients and delivery systems that mediate between the lipophilic CBD and the aqueous GI environment, preventing precipitation and enhancing absorption.
3Ease of manufacture
If amorphous or semi-crystalline cannabidiol is used, then it can be obtained from extraction, but it has poor solubility and is challenging to prepare as a pharmaceutical product
Solution Approach 1:
The patent applies a parameter change in the physical state from amorphous/semi-crystalline to crystalline form. This transformation, achieved through specific crystallization processes, dramatically improves solubility while maintaining the simplicity of obtaining CBD from extraction.
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 crystalline forms provide enhanced stability and processability, allowing for pharmaceutical products that do not require cold storage and improve bioavailability, making them suitable for pharmaceutical compositions.
Implementation Method 1
Form B also has a high melting-point, further improving processability
Data Source
AI summary
The present invention relates to crystalline forms of the synthetic, non-natural cannabinoid (1′R,2′R)-5′-methyl-4-(1-methyl-1H-pyrazol-4-yl)-2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol, methods for their production, and their use in therapy. The crystalline forms are easier to handle than other solid forms, and are useful in the manufacture of medicaments for the treatment of conditions associated with seizure.