Aqueous Gemfibrozil Oral Liquid Formulation for Solubility Stability
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Solution Overview
Problem
Gemfibrozil, a fibrate compound used to treat lysosomal storage disorders and neurodegenerative diseases, has poor solubility in aqueous solutions due to its hydrophobic alkyl-benzene backbone, limiting its effectiveness in liquid formulations.
Innovation Solution
A stable oral liquid pharmaceutical composition of gemfibrozil is formulated using an aqueous solvent with a pH of 10.5, which maintains solubility and stability for at least 36 months, with concentrations ranging from 5 mg/mL to 32 mg/mL, and includes additives like carbonate buffers and preservatives to enhance microbial purity and self-preservation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If gemfibrozil is formulated in traditional organic solvents (ethanol, DMSO, propylene glycol), then solubility is improved (approximately 30-16 mg/ml), but the formulation requires multiple solvents and surfactants, increasing complexity and potential harmful effects
Solution Approach 1:
The patent changes the fundamental parameter of the solvent from organic to aqueous, achieving gemfibrozil solubility in water at concentrations of 5-32 mg/ml. This parameter change eliminates the need for multiple organic solvents and surfactants, thereby reducing formulation complexity while maintaining or improving solubility.
Solution Approach 2:
The patent introduces an intermediary substance (aqueous solvent system with pH 10.5) that mediates between the hydrophobic gemfibrozil molecule and the aqueous environment. This intermediary aqueous phase allows solubility without requiring traditional organic co-solvents, simplifying the overall formulation.
2Quantity of substance
If gemfibrozil is formulated in traditional organic solvents, then solubility is improved, but stability during storage and microbial purity are compromised
Solution Approach 1:
The patent changes the solvent parameter from organic to aqueous with specific pH control (pH 10.5), which simultaneously achieves solubility and enhances stability. The aqueous environment at controlled pH prevents degradation pathways that occur in organic solvents, improving both stability and microbial purity while maintaining acceptable solubility levels.
3Quantity of substance
If gemfibrozil is administered in traditional liquid formulations with multiple solvents, then solubility is achieved, but bioavailability and dissolution performance are limited
Solution Approach 1:
The patent changes the solvent parameter to aqueous with pH 10.5, which improves dissolution performance and bioavailability. The aqueous formulation eliminates the need for multiple solvents, reducing interactions that may hinder dissolution, and provides improved bioavailability while maintaining solubility at 5-32 mg/ml.
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 ensures improved solubility, stability, and bioavailability of gemfibrozil, effectively treating lysosomal storage disorders and neurodegenerative diseases over an extended period.
Implementation Method 1
The gemfibrozil is soluble in the liquid pharmaceutical composition... The solvent is an aqueous buffer having pH 10.5 (+/â0.5)
Data Source
AI summary
In an aspect, the disclosure relates to a liquid pharmaceutical composition comprising, consisting essentially of, or consisting of gemfibrozil and an aqueous solvent. The disclosure also relates to methods of making the liquid pharmaceutical composition comprising gemfibrozil, uses thereof, and methods of treatment comprising administering the liquid pharmaceutical composition comprising gemfibrozil.