Nintedanib Formulation Replacing Lecithin with Non-Ionic Surfactants
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Solution Overview
Problem
Existing nintedanib formulations require lecithin as a glidant for an immediate release profile, which can cause allergic reactions in highly intolerant subjects due to negligible protein amounts.
Innovation Solution
A lipophilic formulation of nintedanib or its pharmaceutically acceptable salt, comprising a non-ionic surfactant and pharmaceutically acceptable excipients such as medium chain triglycerides and hard fat, eliminating the need for lecithin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If lecithin is used as a glidant in nintedanib formulations, then the dissolution rate is increased and immediate release profile is achieved, but allergic reactions may occur in highly intolerant subjects due to negligible protein amounts
Solution Approach 1:
The patent removes lecithin from the formulation composition and replaces it with alternative non-ionic surfactants such as polyglyceryl-3-dioleate, sorbitan monolaurate, or propylene glycol monolaurate. This extraction of the problematic ingredient eliminates the allergic reaction risk while maintaining the desired dissolution rate through the alternative surfactants.
Solution Approach 2:
The patent changes the chemical composition parameter by substituting lecithin with different non-ionic surfactant molecules having different chemical structures but similar functional properties. This parameter change maintains the glidant function for achieving immediate release profile while eliminating the harmful allergic reaction component.
2Reliability
If lecithin is used as the only glidant in nintedanib formulations, then acceptable pharmaceutical properties are achieved, but the formulation complexity is increased due to reliance on a single ingredient
Solution Approach 1:
The patent employs multiple non-ionic surfactants that can each independently provide the glidant function, creating a more versatile formulation system. This multi-functionality approach reduces reliance on a single ingredient and provides flexibility in formulation development while maintaining reliable pharmaceutical properties.
Solution Approach 2:
The patent creates a composite formulation system using combinations of different non-ionic surfactants alongside other excipients such as carriers, thickeners, and solvents. This composite approach distributes the functional requirements across multiple ingredients, reducing the complexity burden on any single component while maintaining overall formulation reliability.
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 achieves an immediate release profile without lecithin, enhancing pharmaceutical properties and reducing the risk of allergic reactions, while maintaining therapeutic efficacy for conditions like non-small cell lung cancer and idiopathic pulmonary fibrosis.
Implementation Method 1
a non-ionic surfactant (glidant, emulsifier)
Implementation Method 2
The only glidant considered is lecithin... presence of lecithin in the formulation is required to increase the dissolution rate
Implementation Method 3
The carrier is preferably a lipid or a lipophilic carrier, more preferably selected from glycerol, acetylated monoglycerides, corn oil glycerides
Implementation Method 4
The formulations as described in WO 2009/147212 comprise a carrier, a thickener and optionally a glidant
Data Source
Figure 1~2
AI summary
The present invention relates to a formulation of nintedanib or a pharmaceutically acceptable salt thereof which contains a non-ionic surfactant. The formulation has an immediate release profile without the need to use lecithin as a surfactant. The formulation is suitable for filling into capsules.