Sildenafil Sublingual Spray Formulation Bypassing Hepatic Metabolism
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Solution Overview
Problem
Current sildenafil formulations for treating erectile dysfunction and pulmonary arterial hypertension have limited bioavailability and delayed onset of action due to hepatic first-pass metabolism, and there is a need for a quick-onset sublingual spray formulation that bypasses these issues.
Innovation Solution
A sublingual spray formulation comprising sildenafil or its salts, solvents like ethanol and glycerin, and a permeation enhancer such as caprylic acid, without propellants, designed to provide improved bioavailability and rapid absorption by optimizing the pH and composition for enhanced permeation through the buccal epithelium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If sildenafil is administered as a film coated tablet, then the formulation is stable and easy to manufacture, but the bioavailability is only 40% and the onset of action is delayed due to hepatic first-pass metabolism
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using sublingual spray delivery with specific pH adjustment (pH 2-6) and solvent composition (ethanol, glycerin, propylene glycol) to enhance drug dissolution and permeation through the buccal epithelium, bypassing hepatic first-pass metabolism and achieving improved bioavailability
Solution Approach 2:
The patent introduces permeation enhancers (caprylic acid, vitamin E TPGS, polysorbates) as intermediary substances that facilitate the transport of sildenafil through the buccal epithelium membrane, enabling rapid absorption into the bloodstream without requiring hepatic metabolism
2Speed
If a sublingual spray formulation is developed to bypass hepatic first-pass metabolism, then bioavailability and onset of action are improved, but the formulation requires multiple components including solvents, permeation enhancers, and pH adjusters
Solution Approach 1:
The patent combines multiple functional components (sildenafil, solvents like ethanol and glycerin, permeation enhancers like caprylic acid, and pH adjusters) into a single integrated sublingual spray formulation that delivers all necessary functions through one administration device, simplifying the patient experience despite the complexity of individual components
3Ease of operation
If propellants are included in the spray formulation to enable delivery, then the spray function is effective, but the formulation may have storage stability issues and requires pressure-liquefied propellant mixtures
Solution Approach 1:
The patent removes propellants from the formulation entirely, using a propellant-free spray delivery system that relies on the viscosity and flow properties of the solvent-based formulation (ethanol, glycerin, propylene glycol) to achieve effective spray delivery without requiring pressure-liquefied propellant mixtures, thereby improving storage stability
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 formulation achieves improved bioavailability, rapid absorption, and storage stability, with enhanced permeation of sildenafil through the buccal epithelium, leading to faster onset of action and increased patient compliance.
Implementation Method 1
enhanced permeation of sildenafil through the buccal epithelium
Implementation Method 2
rapid absorption by optimizing the pH and composition for enhanced permeation through the buccal epithelium
Implementation Method 3
from about 0.1% w/w to about 70% w/w of a solvent selected from the group consisting of water, ethanol, glycerin, polyethylene glycol 400, propylene glycol
Implementation Method 4
from about 0.1% w/w to about 60% w/w of at least one acid, preferably diluted hydrochloric acid, wherein the formulation has a pH from about 2 to about 6
Data Source
AI summary
The invention is directed to sublingual spray formulations containing sildenafil. The invention is further directed to methods of treating male sexual dysfunction or pulmonary arterial hypertension by administering sublingual spray formulations containing sildenafil to patients in need of such treatments.