Amorphous Steroid Tetrol Solid State Forms for Polymorphic Stability
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Solution Overview
Problem
The challenge lies in developing a pharmaceutical formulation of androst-5-ene-3β,7β,16α,17β-tetrol that effectively addresses polymorphism, stability, and bioavailability issues, which are crucial for treating inflammatory and metabolic disorders, as different crystalline forms exhibit varying physical properties affecting efficacy and suitability.
Innovation Solution
A solid state form of androst-5-ene-3β,7β,16α,17β-tetrol is developed, substantially free of other crystalline forms, to enhance stability and bioavailability, which is used in formulations to treat inflammatory, metabolic, and autoimmune conditions by modulating inflammation and metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a chemical substance is used in pharmaceutical formulation, then therapeutic efficacy is achieved, but polymorphism causes unpredictable physical properties affecting stability and bioavailability
Solution Approach 1:
The patent changes the physical state parameter of androst-5-ene-3β,7β,16α,17β-tetrol from conventional crystalline forms to an amorphous solid state form. This parameter change eliminates polymorphism-related unpredictability while maintaining therapeutic efficacy, as the amorphous form provides consistent physical properties for stability and bioavailability.
Solution Approach 2:
The invention utilizes phase transition from crystalline to amorphous state to resolve the polymorphism issue. The amorphous solid state form represents a non-crystalline phase that avoids the multiple crystalline forms (polymorphs) that cause unpredictable physical properties, thereby improving both reliability and stability.
2Ease of manufacture
If crystalline forms are used for pharmaceutical formulation, then manufacturing is straightforward, but different polymorphs exhibit varying physical properties affecting dissolution rate and bioavailability
Solution Approach 1:
The patent changes the physical state from crystalline to amorphous, which simplifies manufacturing by eliminating the need to control and select specific crystalline forms while simultaneously improving bioavailability through consistent dissolution characteristics of the amorphous form.
Solution Approach 2:
The amorphous form can be considered a temporary or intermediate state that is easier to manufacture and provides reliable bioavailability, sacrificing the need for long-term crystalline stability control in favor of manufacturing ease and consistent therapeutic effect.
3Reliability
If metastable crystalline forms are used, then enhanced solubility and bioavailability are achieved, but thermodynamic instability causes conversion to more stable forms over time
Solution Approach 1:
Instead of using metastable crystalline forms that are thermodynamically unstable, the patent changes to an amorphous form that, while not thermodynamically stable in the crystalline sense, provides consistent physical properties and avoids the problem of polymorphic conversion. The amorphous form maintains enhanced solubility and bioavailability without the instability issues of metastable crystals.
Data Source
AI summary
The invention relates to solid state forms of androst-5-ene-3β,7β,16α,17β-triol, formulations containing or prepared from such solid state forms and use of such materials for modulating acute and chronic non-productive inflammation. The formulations can be used to prevent, treat or slow the progression of conditions related to autoimmunity such as arthritis, multiple sclerosis, ulcerative colitis or Type 1 diabetes. The formulations can also be used to prevent, treat or slow the progression of conditions related to metabolic disorders such as Type 2 diabetes.