Bioavailable Solid State (17-β)-Hydroxy-4-Androsten-3-one Esters
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Solution Overview
Problem
Current solid state forms of (17-β)-Hydroxy-4-Androsten-3-one esters face challenges with inadequate solubility and stability, leading to poor bioavailability and inconsistent pharmacokinetic properties, which can affect the efficacy and safety of pharmaceutical formulations.
Innovation Solution
Development of specific solid state forms such as (17-β)-3-Oxoandrost-4-en-17-yl undecanoate, dodecanoate, tridecanoate, and tetradecanoate esters with enhanced solubility and stability, particularly in lipophilic additives, to improve bioavailability and dissolution profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional solid state forms of (17-β)-Hydroxy-4-Androsten-3-one esters are used, then the ester can be formulated for pharmaceutical use, but solubility and stability are inadequate leading to poor bioavailability
Solution Approach 1:
The patent applies parameter changes by developing specific solid state forms (polymorphs) of the ester with optimized physical properties. Different crystal forms were created and characterized to achieve improved solubility and stability parameters, directly addressing the contradiction between formulation capability and bioavailability through physical state modification
Solution Approach 2:
The patent utilizes composite material principles by creating formulated compositions that combine the ester with specific excipients and carriers. These composite formulations were designed to enhance both the stability and solubility of the ester, thereby improving bioavailability while maintaining formulation integrity
2Ease of manufacture
If different solid state forms of the ester are used, then formulation advantages can be achieved, but dissolution profile and pharmacokinetic properties change substantially over time
Solution Approach 1:
The patent applies beforehand cushioning by selecting and stabilizing specific solid state forms that are resistant to polymorphic transformation during storage and formulation. This preventive approach ensures that the dissolution profile and pharmacokinetic properties remain consistent over time, avoiding the problems of form changes while maintaining formulation advantages
Solution Approach 2:
The patent employs the principle of using stable, well-characterized solid state forms that can be reliably reproduced. By focusing on forms with consistent properties, the patent ensures long-term stability of dissolution profiles, avoiding the need for continuous reformulation while maintaining manufacturing advantages
3Ease of manufacture
If the ester changes physical form in the pharmaceutical composition, then processing may be facilitated, but pharmacokinetic properties and safety parameters are affected
Solution Approach 1:
The patent applies beforehand cushioning by pre-stabilizing the ester in specific solid state forms that are resistant to physical transformation during formulation and storage. This prevents form changes that could alter pharmacokinetic properties or safety parameters, while still allowing favorable processing characteristics to be achieved through controlled crystallization or polymorph selection
Solution Approach 2:
The patent employs feedback principles through comprehensive characterization of solid state forms using multiple analytical techniques (XRD, DSC, HPLC) to monitor and control physical form stability. This feedback mechanism ensures that any processing-induced form changes are detected and controlled, maintaining consistent pharmacokinetic properties and safety profiles
Data Source
AI summary
Disclosed are bioavailable solid state (17-β)-Hydroxy-4-Androsten-3-one esters suitable for pharmaceutical uses and administration to mammals in need of (17-β)-Hydroxy-4-Androsten-3-one. Pharmaceutical compositions and the dosage forms of the bioavailable solid state (17-β)-Hydroxy-4-Androsten-3-one esters can be used to treat any condition associated with testosterone deficiency, including complete absence of endogenous testosterone in male or female subjects.