Rasagiline Tartrate Tablet Direct Compression
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Solution Overview
Problem
Current pharmaceutical compositions of rasagiline, particularly in the form of tartrate salt, exhibit poor storage stability and impurity formation due to thermal and acidic processes used in their preparation, which can lead to degradation and reduced efficacy.
Innovation Solution
A pharmaceutical composition of rasagiline tartrate is prepared using a direct compression process without solvents, antioxidants, or acids, utilizing a mixture of microcrystalline cellulose and modified starch as diluents and binders to achieve high storage stability and uniformity, avoiding thermal and acidic conditions that induce degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wet granulation process using water or ethanol is used to prepare rasagiline tartrate tablets, then the tablets can be formed with proper binding, but the storage stability deteriorates and impurity formation increases due to thermal and acidic processes
Solution Approach 1:
The patent changes the physical state parameter of the granulation process from wet (liquid binder) to dry (no liquid binder), eliminating the need for drying and thermal processing. This parameter change resolves the contradiction by improving storage stability while maintaining manufacturability through direct compression.
Solution Approach 2:
The patent extracts and removes the liquid binder component from the granulation process entirely. By eliminating the liquid binder, the wet granulation step and subsequent drying/thermal processes are removed, preventing degradation while still enabling tablet formation through direct compression of the dry mixture.
2Reliability
If mesylate salt of rasagiline is used, then chemical stability is improved, but genotoxic impurities (alkyl mesylates) are formed which are reactive and carcinogenic
Solution Approach 1:
The patent converts the harmful mesylate salt into a beneficial alternative by using tartrate salt instead. This substitution eliminates genotoxic impurity formation while maintaining the desired chemical stability and therapeutic efficacy, turning a harmful formulation approach into a safe one.
Solution Approach 2:
The patent replaces the problematic mesylate salt with a safer tartrate salt formulation. This substitution uses a different chemical entity that achieves the same therapeutic goal without the genotoxic side effects, effectively discarding the harmful approach for a safer alternative.
3Reliability
If direct compression process is used without wet granulation, then storage stability is improved by avoiding thermal processes, but the manufacturing precision and dose uniformity may deteriorate
Solution Approach 1:
The patent applies preliminary action by pre-mixing the rasagiline tartrate with excipients in a dry state before compression. This pre-mixing step ensures homogeneous distribution of the active ingredient, maintaining dose uniformity while avoiding the degradation associated with wet granulation and thermal processing.
Data Source
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AI summary
The present invention relates to a pharmaceutical composition comprising (a) as the active ingredient, rasagiline in the form of pharmaceutically acceptable salt, (b) diluent, (c) lubricant and/or glidant and optionally (d) disintegrant, (e) binder, wherein the composition is not prepared by wet granulation process. The composition is preferably prepared by direct compression.