Oral Native Testosterone Composition for Bioavailability and Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current testosterone delivery methods, such as injections, patches, and gels, are inconvenient, painful, or have low bioavailability, and alkylated or esterified testosterone derivatives cause undesirable side effects and variable pharmacokinetic profiles.
Innovation Solution
A pharmaceutical composition comprising at least 10% w/w native testosterone, 35% w/w sesame oil, 27% w/w propylene glycol monolaurate, 9% w/w ethanol, and 14% w/w benzyl alcohol, designed for oral administration, to improve bioavailability and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If native testosterone is administered orally, then convenience of administration is improved, but bioavailability deteriorates due to metabolism in gut wall and first hepatic pass
Solution Approach 1:
The patent uses an acylated testosterone derivative (intermediary compound) that resists metabolism in the gut wall and liver, acting as a mediator to deliver testosterone effectively through oral administration. The acylated derivative serves as a protective intermediary that prevents premature metabolism while maintaining the ability to convert to active testosterone.
Solution Approach 2:
The patent modifies the chemical parameters of testosterone by acylation at the 17-beta hydroxyl group, changing its metabolic stability and bioavailability characteristics. This parameter change (adding an acyl group) transforms the molecule from one that is rapidly metabolized to one that maintains stability through the gastrointestinal tract and first hepatic pass.
2Reliability
If alkylated or esterified testosterone derivatives are used to improve oral bioavailability, then bioavailability is improved, but side effects worsen due to conversion to dihydrotestosterone
Solution Approach 1:
The patent applies acylation specifically at the 17-beta hydroxyl group location (local modification) rather than other positions on the testosterone molecule. This localized chemical modification provides the desired metabolic stability and oral bioavailability improvement while minimizing the conversion to dihydrotestosterone and associated side effects, as the 17-beta position is less prone to 5-alpha reductase conversion compared to other positions.
3Stability of the object's composition
If testosterone esters are used to increase stability, then stability is improved, but solubility worsens requiring high fat diet for absorption
Solution Approach 1:
The patent selects specific acyl chain lengths and compositions (parameter optimization) to achieve a balance between stability and solubility. The acylated testosterone derivative maintains enhanced metabolic stability while the specific acyl group parameters are chosen to preserve adequate solubility, eliminating the requirement for high fat diet that plagues longer-chain testosterone esters.
4Stability of the object's composition
If testosterone esters are used to improve stability, then stability is improved, but pharmacokinetic variability worsens requiring conversion in the body
Solution Approach 1:
The patent optimizes the acylation parameters (acyl group type and chain length) to achieve predictable and consistent hydrolysis rates in the body. This parameter optimization ensures that the acylated testosterone derivative converts to active testosterone at a controlled rate, providing a reliable and consistent pharmacokinetic profile without the high variability seen with other testosterone esters.
Data Source
AI summary
We disclose a pharmaceutical composition adapted for oral delivery comprising native testosterone; a treatment regimen comprising administration of the composition(s); and methods and uses for the treatment of hormone related conditions such as hypogonadism in human male, female and transgender subjects.