Anhydrous Lenalidomide Form I Stable Composition
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Solution Overview
Problem
Current pharmaceutical compositions of Lenalidomide face challenges such as thermal decomposition during melt extrusion, low solubility in solvents for spray drying, and the use of toxic solvents, leading to instability and inefficiencies in preparing stable dosage forms.
Innovation Solution
A stable composition comprising anhydrous Lenalidomide Form I combined with lactose anhydrous, which maintains stability and bioavailability, and is formulated into capsules with reduced excipient content, allowing for improved patient compliance and reduced capsule size.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If melt extrusion is used to prepare Lenalidomide solid solutions, then the solid solution can be obtained, but thermal decomposition occurs due to high temperatures required for Lenalidomide with high melting point
Solution Approach 1:
The patent changes the physical state parameter of Lenalidomide from crystalline to amorphous form, which has lower melting point and avoids thermal decomposition during melt extrusion. This parameter change enables solid solution preparation without the harmful thermal effects that occur with crystalline forms.
Solution Approach 2:
The patent creates composite materials by forming solid solutions of amorphous Lenalidomide with polymer matrices. This composite approach allows the drug to be processed at lower temperatures while maintaining stability and solubility benefits.
2Ease of manufacture
If spray drying is used to prepare Lenalidomide solid solutions, then the solid solution can be obtained, but copious amounts of solvents are required due to low solubility of Lenalidomide in spray drying solvents
Solution Approach 1:
The patent changes the solubility parameter by using amorphous Lenalidomide instead of crystalline form. The amorphous state has significantly higher solubility in organic solvents, allowing spray drying to be performed with much smaller amounts of solvent while still achieving complete dissolution and stable solid solutions.
3Ease of manufacture
If amorphous Lenalidomide dispersions are prepared using dimethylformamide and methanol, then the dispersion can be obtained, but toxic solvents are used which are undesirable for pharmaceutical products
Solution Approach 1:
The patent changes the solvent selection by utilizing the enhanced solubility of amorphous Lenalidomide in less toxic solvents. The amorphous form's superior solubility characteristics allow the use of safer pharmaceutical excipients and solvents while maintaining effective dispersion preparation.
4Reliability
If high temperatures are used for spray drying to remove solvents completely, then solvent removal is achieved, but thermal decomposition may occur
Solution Approach 1:
The patent changes the drying temperature parameter by utilizing the improved solvent evaporation characteristics of amorphous Lenalidomide dispersions. The amorphous form allows for lower temperature processing while achieving complete solvent removal, thus avoiding thermal decomposition.
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising Lenalidomide. More particularly, the present invention relates to a stable composition comprising anhydrous Lenalidomide Form I and one or more pharmaceutically acceptable excipients and process for preparing such compositions.