Terlipressin Aqueous Formulation With pH-Controlled Stability
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Solution Overview
Problem
Current terlipressin formulations require refrigeration and complex preparation steps, limiting their use to hospital settings and posing risks due to short half-life and side effects, necessitating a stable, room temperature-compatible formulation for outpatient and rapid use.
Innovation Solution
Aqueous compositions of terlipressin acetate with pH 3.4 to 5.0, including stabilizing agents like aspartic acid, are developed for pre-filled syringes, providing stability up to 2 years at room temperature and reducing impurities to less than 4.5%, suitable for continuous infusion or bolus administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If terlipressin is formulated as lyophilized powder or liquid solution requiring refrigeration, then stability is maintained, but storage and administration complexity increases and accessibility decreases
Solution Approach 1:
The patent changes the pH parameter of the terlipressin solution to a specific range (3.0-5.0) and adjusts the concentration to 0.1-10 mg/mL, which enables the formulation to achieve both stability and room temperature storage capability, eliminating the need for refrigeration and complex preparation steps
Solution Approach 2:
The patent provides terlipressin in a pre-filled syringe format with the solution already prepared at the correct pH and concentration, eliminating the need for healthcare workers to perform reconstitution or mixing steps before administration
2Reliability
If terlipressin is administered as IV bolus every 4-6 hours, then therapeutic effect is achieved, but treatment frequency increases and patient comfort decreases
Solution Approach 1:
The patent enables continuous subcutaneous infusion of terlipressin over 24 hours, providing continuous therapeutic action and maintaining steady drug levels in the body, which eliminates the need for repeated IV bolus administrations every 4-6 hours and improves patient comfort while maintaining therapeutic effectiveness
3Productivity
If terlipressin concentration is increased to reduce injection frequency, then productivity improves, but stability and purity maintenance becomes more difficult
Solution Approach 1:
The patent optimizes the pH parameter to a specific range (3.0-5.0) and the concentration to 0.1-10 mg/mL, which allows the formulation to remain stable and pure even at higher concentrations that enable less frequent administration, thus improving productivity without sacrificing 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 compositions maintain terlipressin's stability and efficacy at room temperature, simplifying administration and expanding use to outpatient settings without refrigeration needs, while minimizing side effects and impurity formation.
Implementation Method 1
wherein the pH of the composition is from about 3.4 to about 5.0
Implementation Method 2
the composition comprises a stabilizing agent
Data Source
AI summary
The disclosure provides pharmaceutical compositions comprising terlipressin having increased concentration with long term storage stability.