Lenalidomide Liquid Composition Stability via Excipient Mediation
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Solution Overview
Problem
Current extemporaneous preparations of lenalidomide in liquid form lack stability and consistency, leading to variable drug content and poor patient compliance due to incomplete dissolution and instability issues.
Innovation Solution
A pharmaceutical composition of 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperidine-2, 6-dione in a liquid form, dissolved with pharmaceutically acceptable excipients such as Poly Ethylene Glycol 400, Propylene Glycol, and Butylated Hydroxyanisole, ensuring stability and complete solubility, with a process involving homogenization to maintain impurity levels below 0.5% after storage at 2-8°C.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If extemporaneous liquid preparation of lenalidomide is prepared by dissolving capsule contents in water, then liquid dosage form is achieved, but the preparation lacks stability and shows variable drug content
Solution Approach 1:
The patent introduces specific excipients (hydroxypropyl methylcellulose, polyethylene glycol, propylene glycol, butylated hydroxyanisole) as intermediary substances to mediate between the drug and the aqueous environment. These excipients form a stable liquid matrix that maintains drug solubility and prevents degradation, resolving the instability issue while preserving the liquid dosage form advantage
Solution Approach 2:
The patent modifies the chemical and physical parameters of the liquid preparation by controlling pH (using glacial acetic acid), adjusting composition ratios of multiple excipients, and setting specific storage conditions (2-8°C). These parameter changes transform an unstable extemporaneous preparation into a stable formulated product with consistent drug content
2Ease of operation
If lenalidomide is dissolved in water for liquid preparation, then administration is simplified, but incomplete dissolution occurs leading to variable drug content
Solution Approach 1:
The patent creates a composite liquid formulation combining lenalidomide with multiple excipients (hydroxypropyl methylcellulose, polyethylene glycol, propylene glycol, glacial acetic acid, and butylated hydroxyanisole). This composite system ensures complete drug dissolution through synergistic interactions among components, eliminating the incomplete dissolution problem while maintaining liquid form for easy administration
Solution Approach 2:
The excipients act as intermediary substances that facilitate complete drug dissolution. Hydroxypropyl methylcellulose and polyethylene glycol serve as solubilizing agents that prevent drug precipitation, ensuring uniform drug distribution and consistent dosing throughout the liquid preparation
3Device complexity
If simple extemporaneous preparation method is used, then preparation complexity is reduced, but impurity levels increase and stability decreases
Solution Approach 1:
The patent incorporates butylated hydroxyanisole as a preservative and antioxidant in the formulation before preparation. This preliminary inclusion of stabilizing agents prevents impurity formation during storage without requiring complex post-preparation processing steps, thus maintaining low impurity levels while keeping the preparation process relatively simple
Solution Approach 2:
The patent specifies precise formulation parameters including pH adjustment with glacial acetic acid and controlled storage temperature (2-8°C). These parameter specifications prevent chemical degradation and impurity formation during storage, achieving low impurity levels through controlled formulation rather than complex processing
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 composition provides a stable and effective liquid dosage form of lenalidomide with reduced impurities, ensuring consistent drug delivery and improved patient compliance, maintaining stability and solubility over time.
Implementation Method 1
Butylated Hydroxyanisole (0.01 to 3% w/w), more preferably 0.1 to 1% w/w
Implementation Method 2
pharmaceutically acceptable excipients such as Poly Ethylene Glycol 400, Propylene Glycol
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperidine-2, 6-dione dissolved in a liquid vehicle. The present invention also relates to pharmaceutical compositions comprising 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperidine-2, 6-dione and one or more pharmaceutically acceptable excipients. The present invention also related to the process for preparing the said liquid composition and its use for treating multiple myeloma and lymphoma.