Crystalline (17-β)-3-Oxoandrost-4-en Dodecanoate for Bioavailability
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Solution Overview
Problem
Existing solid state forms of (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate esters exhibit inadequate solubility, release, dissolution, and physical stability, leading to poor bioavailability and absorption of (17-β)-Hydroxy-4-Androsten-3-one, which is crucial for treating conditions like male or female hypogonadism, lung disease, and liver disease.
Innovation Solution
Development of a specific crystalline solid state form of (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate that dissolves at least 0.001% in a 8% Triton X100 aqueous solution within 30 minutes at 37°C, ensuring stable and bioavailable administration of (17-β)-Hydroxy-4-Androsten-3-one.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate are used, then the compound can be administered, but solubility, release, dissolution, and physical stability are inadequate leading to poor bioavailability
Solution Approach 1:
The patent changes the physical state parameter from amorphous or unstable crystalline forms to a specific stable crystalline form with defined polymorphic structure. This parameter change resolves the contradiction by establishing both physical stability and reliable bioavailability through controlled crystal packing and molecular arrangement.
Solution Approach 2:
The patent utilizes phase transition control to establish a specific crystalline form that is stable under storage conditions but releases the active ingredient reliably. The controlled phase behavior of the ester compound enables both physical stability during storage and reliable bioavailability during administration.
2Productivity
If existing solid state forms are used, then administration is possible, but dissolution and release rate are insufficient
Solution Approach 1:
The patent modifies the crystalline structure parameters to achieve optimal balance between stability and dissolution rate. By controlling crystal size, polymorphic form, and molecular packing density, the compound maintains crystalline stability while achieving adequate dissolution and release rates for effective administration.
3Ease of manufacture
If the solid state form changes over time, then processing may be easier, but pharmacokinetic properties change altering efficacy and safety
Solution Approach 1:
The patent establishes a specifically stable crystalline form before administration that is resistant to polymorphic transformation during storage and processing. This pre-established stable form cushions against unwanted changes, maintaining consistent pharmacokinetic properties while allowing for ease of manufacture through controlled crystallization processes.
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 form provides enhanced bioavailability and sustained release of (17-β)-Hydroxy-4-Androsten-3-one, addressing the stability and absorption issues of previous forms, thereby improving therapeutic efficacy for conditions such as hypogonadism, lung disease, and liver disease.
Implementation Method 1
a solid state form of (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate having a dissolution rate of at least about 0.001% in a 8% Triton X100 aqueous solution in 30 minutes at 37° C.
Data Source
AI summary
Disclosed are bioavailable solid state (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate compositions and methods of use in administration to mammals in need of thereof. The (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate is preferably provided in a solid state crystalline form having a plurality of peaks corresponding to the peaks shown in FIG. 2, a plurality of crystallites ranging in size from about 40 nm to about 60 nm based as identified via powder x-ray diffraction spectra, and a melting point in the range of about 51° C. to about 63° C. The compositions may be provided in oral or injectable administration form for the treatment of conditions such as in need of testosterone therapy. An exemplary chemical structure of a (17-β)-3-Oxoandrost-4-en-17-yl dodecanoate composition disclosed herein is as follows: