Organic-Aqueous Formulation for Mucosal Permeation
Solution Overview
Problem
Current treatments for erectile dysfunction, particularly those involving phosphodiesterase inhibitors like sildenafil, tadalafil, and vardenafil, face challenges with low aqueous solubility at physiological pH, limiting their effectiveness when administered sublingually or intranasally due to poor permeation and absorption across mucosal membranes.
Innovation Solution
Development of organic-aqueous mixtures containing alcohols, polyethers, and glycerides that enhance the solubility and permeation of phosphodiesterase inhibitors across mucosal membranes by adjusting the pH to between 3.5 and 8.0, thereby improving bioavailability and absorption rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If phosphodiesterase inhibitors are administered orally, then they can be delivered to the body, but the onset is slow and bioavailability is limited due to first-pass metabolism
Solution Approach 1:
The patent uses organic-aqueous mixtures containing penetration enhancers (such as surfactants, alcohols, or fatty acids) as intermediaries to facilitate the transfer of phosphodiesterase inhibitors across the mucosal membrane. These penetrants modify the membrane properties or interact with the drug to enhance its permeation, enabling rapid absorption through the nasal or sublingual routes while maintaining high bioavailability without relying on oral administration pathways subject to first-pass metabolism.
2Quantity of substance
If the formulation uses pure aqueous solution, then it is safe and well-tolerated, but the solubility of phosphodiesterase inhibitors is insufficient
Solution Approach 1:
The patent modifies the physical and chemical parameters of the formulation by adjusting pH levels, ionic strength, and organic content to optimize both solubility and safety. By carefully controlling these parameters, the formulation achieves adequate solubility of phosphodiesterase inhibitors while maintaining a pH range and composition that is compatible with mucosal tissues, thereby avoiding irritation or toxicity.
Solution Approach 2:
The patent employs composite formulations consisting of organic-aqueous mixtures that combine the benefits of both organic solvents (enhanced solubility) and aqueous solutions (safety and tolerability). These composite systems use synergistic combinations of penetrants, surfactants, and co-solvents to achieve high drug solubility while maintaining biocompatibility and minimizing adverse effects on the mucosal membrane.
3Quantity of substance
If organic solvents are used to enhance solubility, then the solubility of phosphodiesterase inhibitors improves, but the safety and tolerability decrease
Solution Approach 1:
The patent optimizes the concentration and type of organic components by adjusting formulation parameters such as pH, ionic strength, and organic solvent content. This allows achieving sufficient solubility enhancement while keeping the organic component levels below thresholds that would cause mucosal irritation or toxicity, thus balancing solubility improvement with safety maintenance.
Solution Approach 2:
The patent introduces safe penetrants and surfactants as intermediaries that enable solubility enhancement without requiring high concentrations of potentially harmful organic solvents. These intermediary substances facilitate drug dissolution and membrane permeation through alternative mechanisms, reducing the need for aggressive organic solvents while maintaining effective solubility enhancement.
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 proposed formulations significantly increase the solubility and permeation of phosphodiesterase inhibitors, leading to faster onset and higher bioavailability when administered intranasally or sublingually, compared to traditional oral administration.
Implementation Method 1
an organic-aqueous solvent enhances solubility of the one or more phosphodiesterase inhibitor relative to solubility of the one or more phosphodiesterase inhibitor in water
Implementation Method 2
formulations for enhancing solubility/permeation of one or more phosphodiesterase inhibitor across a mucosal membrane
Data Source
AI summary
The formulation disclosed herein has beneficial properties in enhancing the solubility and permeability (flux) of at least one of vardenafil, sildenafil, and/or related phosphodiesterase inhibitors or other ionizable compounds. In particular, the formulation confers beneficial properties for compounds in crossing the mucosal membrane, leading to an effective plasma drug concentration. In some embodiments, the formulation comprises an organic-aqueous solvent, which may include at least one of an alcohol, a polyether, diethylene glycol monoethyl ether, a medium chain glyceride, one or more saturated polyglycolyzed C8-C10 glyceride, and/or organic salts, or any combination thereof. In some embodiments, the formulation has a pH of about 3.5 to about 8.0. Also disclosed herein is a use for the formulation in administering one or more compound for the treatment of erectile dysfunction or other diseases, wherein the one or more compound is administered transmucosally (intranasally or sublingually).