Self-Emulsifying Formulations for Testosterone Lymphatic Absorption

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Solution Overview

Problem

Existing drug delivery systems for lipophilic drugs like testosterone undecanoate face challenges such as rapid metabolism, variable absorption, significant food effects, and inadequate bioavailability due to first-pass metabolism and poor water solubility, leading to inconsistent pharmacokinetic profiles and potential side effects.

Innovation Solution

The development of self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), and self-nanoemulsifying drug delivery systems (SNEDDS) formulations that include phytosterols and phytosterol fatty acid esters, along with specific surfactants, to enhance solubility, stability, and absorption, minimizing food effects and improving pharmacokinetic profiles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If lipophilic drugs are administered orally, then ease of administration is improved, but bioavailability is reduced due to first-pass metabolism

Engineering Contradiction:

Improveease of administrationVSAvoidbioavailability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent uses self-emulsifying excipients as intermediaries that facilitate lymphatic transport of testosterone undecanoate, bypassing hepatic first-pass metabolism. The emulsifying system acts as a mediator between the lipophilic drug and the lymphatic absorption pathway, enabling oral administration while avoiding metabolic degradation in the liver.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If higher doses are administered to overcome poor water solubility, then drug absorption is improved, but side effects increase

Engineering Contradiction:

Improvedrug absorptionVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the physical-chemical parameters of the drug delivery system by formulating testosterone undecanoate in self-emulsifying excipients with specific HLB values and lipid compositions. This parameter change enables the lipophilic drug to form stable emulsions that enhance solubility and absorption without requiring higher doses, thereby avoiding dose-related side effects.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If conventional emulsion formulations are used, then drug solubility is improved, but absorption variability increases due to food effects

Engineering Contradiction:

Improvedrug solubilityVSAvoidabsorption consistency

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies local quality by selecting excipients with specific properties (HLB values, lipid types) that create localized emulsion characteristics optimized for lymphatic absorption. The self-emulsifying system creates a localized delivery mechanism that is less influenced by gastric emptying and food composition, reducing absorption variability compared to conventional emulsions.

Inventive Principle:

Principle #3Local quality

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

These formulations achieve fast and extended release of testosterone undecanoate with reduced DHT/T ratios, maintaining steady-state serum testosterone levels within the normal range, minimizing food effects, and enhancing lymphatic absorption, thereby improving therapeutic efficacy and reducing side effects.

Implementation Method 1

self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), and self-nanoemulsifying drug delivery systems (SNEDDS) formulations that include phytosterols and phytosterol fatty acid esters, along with specific surfactants, to enhance solubility

Methodology Applied

Scientific EffectSolubilization: Solvation

Implementation Method 2

Methodology Applied

Scientific EffectSurface tension reduction: Surfactant

Implementation Method 3

The lymphatic system is an extensive drainage network spread throughout the body. It shadows the blood circulation system and its functions include the transport of fluid components of blood which have passed into the interstitial space from the capillaries of the circulation system. The intestinal lymphatic system also plays an essential role in absorption of products from lipid digestion

Methodology Applied

Scientific EffectLymphatic absorption: Absorption (physical)

Data Source

PatentUS12357643B2Emulsion formulations

Publication Date: 2025.07.15 MARIUS PHARMACEUTICALS LLC

AI summary

A SEDDS or SMEDDS or SNEDDS formulation for drug delivery of a lipophilic therapeutic agent, providing enhanced modulation of solubility, stability, absorption, metabolism, and/or pharmacokinetic profile of the therapeutic agent by formulation with a lipophilic surfactant, a hydrophilic surfactant, one or more solubilizers and, optionally, digestible oils, resulting in higher bioavailability of the therapeutic agent administered to a subject in need of such therapeutic agent. Also described are pharmaceutical compositions containing the formulations and methods of making and methods of using the formulations and pharmaceutical compositions. Formulations of the disclosure can be constituted to minimize the synthesis of dihydrotestosterone when the therapeutic agent includes testosterone or testosterone esters.