Non-aqueous Solvent Formulations for Stable Parenteral Injection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pharmaceutical formulations of small molecule drugs face challenges with limited solubility and stability in aqueous environments, leading to difficulties in parenteral administration, such as large dosage volumes and the need for reconstitution or dilution before injection.
Innovation Solution
A stable liquid formulation is developed that solubilizes small molecule drugs in a non-aqueous environment, allowing direct parenteral injection without reconstitution or dilution, using biocompatible non-aqueous solvents like DMSO and NMP, which increases solubility and stability, enabling smaller dosage volumes and extended shelf-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If aqueous formulations with co-solvents are used to solubilize small molecule drugs, then solubility is improved, but dosage volume increases and stability deteriorates
Solution Approach 1:
The patent changes the fundamental parameter of the solvent system from aqueous to non-aqueous (using biocompatible solvents like DMSO, NMP, ethyl acetate, or their mixtures). This parameter change enables high drug solubility (e.g., diazepam at 500 mM or higher) while maintaining small dosage volumes suitable for parenteral injection, directly resolving the contradiction between solubility and dosage volume.
2Adaptability or versatility
If aqueous formulations are used for parenteral injection, then compatibility with body environment is improved, but drug stability deteriorates
Solution Approach 1:
The patent applies preliminary protection by formulating the drug in a non-aqueous environment that inherently stabilizes the drug molecule before administration. The biocompatible non-aqueous solvent system provides a stable formulation that prevents degradation, and the formulation is designed to be compatible with parenteral administration without requiring reconstitution, thus maintaining stability while ensuring environmental compatibility.
3Stability of the object's composition
If lyophilized powders are used to improve shelf-life, then stability is improved, but ease of operation deteriorates due to reconstitution requirement
Solution Approach 1:
The patent creates a stable, ready-to-use liquid formulation in biocompatible non-aqueous solvents that does not require reconstitution. The formulation is designed to be stable enough for extended shelf-life while maintaining liquid form for direct injection, eliminating the need for reconstitution steps and improving ease of operation without sacrificing stability.
4Quantity of substance
If large-volume intramuscular injection is used to deliver sufficient drug dose, then drug delivery is improved, but ease of operation deteriorates due to injection difficulty and pain
Solution Approach 1:
The patent changes the solvent system parameter to biocompatible non-aqueous solvents, which enables high drug concentration (e.g., 500 mM diazepam or higher). This allows delivery of sufficient therapeutic doses in small injection volumes (e.g., 1-3 mL or less), making intramuscular injection feasible and comfortable for convulsing patients while delivering the required drug quantity.
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
This approach provides a more stable and efficient delivery method for small molecule drugs, allowing for smaller, more convenient injection volumes and eliminating the need for reconstitution or dilution, enhancing the administration of life-saving drugs like diazepam and other small molecule compounds.
Implementation Method 1
a stable liquid formulation for parenteral injection comprising a small molecule drug, or a salt thereof and a biocompatible non-aqueous solvent, wherein the small molecule drug is solubilized within the non-aqueous solvent
Data Source
AI summary
Disclosed is a stable liquid formulation for parenteral injection comprising a biocompatible non-aqueous solvent and a small molecule drug, or a salt thereof, solubilized within the non-aqueous solvent, wherein the liquid formulation comprises less than 10% by weight residual water, and wherein the volume of the liquid formulation to be parenterally injected is from 0.1 μl to 3 ml.