Testosterone Undecanoate Solid Oral Dosage Form Bioavailability
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Solution Overview
Problem
Current testosterone therapy options, particularly oral delivery forms, face challenges such as poor bioavailability, short serum half-life, and liver-related issues due to first-pass metabolism, leading to the need for high doses and frequent administration, as well as limitations in capsule size and manufacturing complexity for testosterone undecanoate formulations.
Innovation Solution
Development of solid oral dosage forms containing testosterone undecanoate with a pharmaceutically acceptable carrier that releases at least 35 wt % of the drug within 120 minutes, formulated to provide sustained release and improved bioavailability without forming oil-in-water emulsions, and excluding lipid substances to address solubility and stability issues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral testosterone undecanoate is formulated in liquid carrier capsules, then bioavailability is improved, but capsule size is limited and manufacturing complexity increases
Solution Approach 1:
The patent changes the physical state parameter of testosterone undecanoate from liquid to solid form. This fundamental parameter change enables the formulation to be processed using standard solid dosage manufacturing techniques while maintaining the drug's bioavailability characteristics, thereby resolving the contradiction between improved bioavailability and manufacturing complexity
Solution Approach 2:
The patent creates a composite formulation by combining solid testosterone undecanoate with specific solid carriers and excipients. This composite approach allows the formulation to achieve both the desired bioavailability and manufacturability, as the solid carrier system provides structural integrity for standard capsule filling while enabling controlled drug release
2Reliability
If high doses of oral testosterone are administered to overcome poor bioavailability, then therapeutic effectiveness is improved, but liver-related harmful effects increase
Solution Approach 1:
The patent modifies the formulation parameters of testosterone undecanoate to enhance its absorption characteristics. By optimizing the solid formulation composition and release profile, the drug achieves therapeutic effectiveness at lower doses, thereby reducing the metabolic burden on the liver and minimizing harmful effects
Solution Approach 2:
The patent introduces solid carriers and excipients as intermediaries that facilitate the absorption and release of testosterone undecanoate. These intermediary substances improve the drug's bioavailability and reduce first-pass metabolism, allowing lower doses to achieve therapeutic effects and thereby reducing liver-related harmful effects
3Reliability
If testosterone undecanoate is formulated with lipid substances to improve solubility, then bioavailability is improved, but oxidative instability increases
Solution Approach 1:
The patent changes the formulation from lipid-based to solid-based system. This parameter change eliminates the oxidative instability associated with lipid substances while maintaining drug solubility and bioavailability through the solid carrier matrix, thereby resolving the contradiction between improved bioavailability and reduced oxidative instability
Solution Approach 2:
The patent employs solid excipients and carriers that are stable and non-reactive, replacing unstable lipid substances. These solid components provide the necessary solubility enhancement without introducing oxidative instability, ensuring formulation stability while maintaining bioavailability
Data Source
AI summary
The present disclosure is drawn to pharmaceutical compositions and oral dosage forms containing testosterone undecanoate, as well as related methods of treatment. In one embodiment, the oral dosage form can include a therapeutically effective amount of testosterone undecanoate and a pharmaceutically acceptable carrier. The dosage form can be formulated such that, when measured using a USP Type II apparatus in 1000 mL of 8 wt % Triton X-100 in water at 37° C. and 100 rpm, the oral dosage form releases at least 20% more testosterone undecanoate after the first 120 minutes than an equivalent dose testosterone undecanoate containing oral dosage form without the pharmaceutically acceptable carrier.