Concentrated Furosemide Formulation for Stable Subcutaneous Delivery
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Solution Overview
Problem
Furosemide's oral bioavailability is limited due to solubility and stability issues, necessitating intravenous administration, which requires trained professionals, while subcutaneous administration is hindered by discomfort and formulation instability.
Innovation Solution
Development of a liquid pharmaceutical formulation of furosemide with concentrations ranging from 40 mg/mL to 250 mg/mL, pH 6.5 to 8.5, using pharmaceutically acceptable excipients and buffers to enhance stability and reduce discomfort during subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravenous administration is used to ensure effective furosemide delivery, then therapeutic efficacy is improved, but device complexity and operational difficulty increase due to requirement for trained healthcare professionals
Solution Approach 1:
The patent enables patients or caregivers to administer the medication themselves through subcutaneous injection, eliminating the need for trained healthcare professionals. The formulation is designed to be safe for self-administration with appropriate training, allowing individuals to manage their own therapy at home.
Solution Approach 2:
The patent introduces a subcutaneous administration route as an intermediary between intravenous (requiring professionals) and oral (poor bioavailability) routes. This intermediate route provides effective drug delivery while being suitable for self-administration, thus resolving the contradiction between efficacy and ease of operation.
2Ease of operation
If subcutaneous administration is implemented to improve ease of operation, then patient compliance is improved, but pain and discomfort increase during administration
Solution Approach 1:
The patent modifies the formulation parameters including pH (adjusted to reduce pain), osmolality (isotonic or hypotonic to minimize discomfort), and concentration (40-250 mg/mL) to optimize the injection experience. These parameter changes reduce pain and discomfort while maintaining ease of self-administration.
Solution Approach 2:
The formulation is specifically designed with local quality considerations for subcutaneous tissue compatibility. The pH and osmolality are adjusted to match physiological conditions, creating a locally appropriate formulation that minimizes tissue irritation and pain at the injection site.
3Volume of moving object
If furosemide concentration is increased to reduce injection volume, then administration comfort is improved, but formulation stability deteriorates due to pH and solubility limitations
Solution Approach 1:
The patent achieves high concentration (40-250 mg/mL) while maintaining stability by carefully controlling pH (6.5-8.5) and adding stabilizing excipients. This parameter optimization allows concentrated formulation that reduces injection volume while preventing drug degradation and precipitation.
Solution Approach 2:
The patent uses composite formulation containing furosemide combined with stabilizing excipients and buffers. This composite approach maintains drug stability at high concentrations by creating a synergistic system where excipients protect furosemide from pH-related degradation and precipitation.
4Ease of operation
If oral administration is used to improve ease of operation, then patient compliance is improved, but therapeutic efficacy decreases due to limited bioavailability from solubility and stability issues
Solution Approach 1:
The patent positions subcutaneous administration as an intermediary route between oral (convenient but ineffective) and intravenous (effective but complex) routes. This intermediate route provides both good bioavailability and ease of self-administration, resolving the contradiction between convenience and efficacy.
Solution Approach 2:
The patent enables patients to self-administer the medication at home through subcutaneous injection, combining the convenience of self-service with effective drug delivery. This eliminates the need for healthcare professional involvement while maintaining therapeutic efficacy.
Data Source
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.