Concentrated Furosemide Formulation for Comfortable Subcutaneous Dosing

Solution Overview

Problem

Furosemide's oral bioavailability is limited due to solubility and stability issues at acidic pH, necessitating intravenous administration, which requires trained professionals, while subcutaneous administration is hindered by discomfort and pain, requiring improved formulations for self-administration.

Innovation Solution

Development of liquid pharmaceutical formulations containing furosemide with concentrations ranging from 40 mg/mL to 250 mg/mL, pH 6.5 to 8.5, using pharmaceutically acceptable excipients and buffers like benzyl alcohol, N-methyl-pyrrolidone, and tromethamine to enhance stability and reduce discomfort.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If intravenous administration is used to ensure reliable drug delivery, then therapeutic efficacy is improved, but device complexity and operational difficulty increase due to requirement of trained healthcare professionals

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidadministration complexity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent introduces a subcutaneous injection device as an intermediary tool that enables patients to administer furosemide themselves. The device includes a disposable syringe with pre-filled formulation and a reusable pump unit, allowing self-administration without requiring trained healthcare professionals while maintaining reliable drug delivery through controlled subcutaneous injection.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent enables patients to self-administer furosemide through a user-friendly subcutaneous injection system. The formulation is designed specifically for subcutaneous delivery, and the injection device is configured to be easily operated by patients at home, eliminating the need for frequent visits to healthcare facilities and empowering patients to manage their own therapy.

Inventive Principle:

Principle #25Self-service

2Ease of operation

If subcutaneous administration is implemented to improve ease of operation, then patient self-administration is enabled, but pain and discomfort increase during administration

Engineering Contradiction:

Improveself-administration capabilityVSAvoidpain and discomfort

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the formulation parameters of furosemide by adjusting pH to a neutral or slightly alkaline range (7.0-8.5) and optimizing osmolality to be isotonic or hypotonic with respect to blood. These parameter changes reduce irritation and pain at the injection site, making subcutaneous administration more comfortable for patients while maintaining therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces a subcutaneous injection device as an intermediary tool that enables patients to administer furosemide themselves. The device includes a disposable syringe with pre-filled formulation and a reusable pump unit, allowing self-administration without requiring trained healthcare professionals while maintaining reliable drug delivery through controlled subcutaneous injection.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If furosemide concentration is increased to reduce administration frequency, then productivity is improved, but solubility and stability at acidic pH deteriorate

Engineering Contradiction:

Improveadministration frequencyVSAvoiddrug stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent modifies the formulation parameters of furosemide by adjusting pH to a neutral or slightly alkaline range (7.0-8.5) and optimizing osmolality to be isotonic or hypotonic with respect to blood. These parameter changes reduce irritation and pain at the injection site, making subcutaneous administration more comfortable for patients while maintaining therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

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 formulations provide a stable, isotonic, and pH-balanced solution for subcutaneous administration, minimizing pain and enabling self-administration by patients or caregivers, optimizing pharmacokinetic profiles.

Implementation Method 1

a pharmaceutically acceptable buffer, wherein the concentration of furosemide in the liquid pharmaceutical formulation is from about 40 mg/mL to about 250 mg/mL. In certain embodiments, the pH of the liquid pharmaceutical formulation is from about 6.5 to about 8.5

Methodology Applied

Scientific EffectpH buffering:

Implementation Method 2

the formulations provide a stable, isotonic, and pH-balanced solution for subcutaneous administration, minimizing pain

Methodology Applied

Scientific EffectOsmotic pressure balance: Osmotic Pressure

Data Source

PatentUS12491196B2Concentrated liquid pharmaceutical formulations of furosemide and methods of administering the same

Publication Date: 2025.12.09 MANNKIND CORP

AI summary

Disclosed herein, in part, are liquid pharmaceutical formulations comprising furosemide or a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable excipients, and a pharmaceutically acceptable buffer. Methods of treating congestion, edema, fluid overload, or hypertension in a patient in need thereof are also provided.