Mannitol Granules Direct Compression Lubricant Reduction
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Solution Overview
Problem
Existing direct compression techniques for tablet production require high amounts of lubricants like magnesium stearate, which can slow disintegration and dissolution, have an unpleasant taste, and are costly, and previous solutions using mannitol and granular starch face issues with bacterial contamination and stability.
Innovation Solution
Development of mannitol granules in both α and β crystalline forms with a specific size range and aerated density, produced through a multiple-effect atomization process, that are essentially free of granular starch, allowing for reduced lubricant usage and improved compressibility and flow properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high quantities of lubricant (magnesium stearate) are used in direct compression, then tablet ejection and integrity are improved, but disintegration and dissolution are slowed
Solution Approach 1:
The patent extracts and removes granular starch from the excipient composition, using only mannitol as the direct compression excipient. This eliminates the harmful effects of starch (bacterial contamination, water sensitivity) while maintaining the necessary lubricant quantities for tablet integrity without excessive disintegration delay
Solution Approach 2:
The patent changes the physical parameters of mannitol by controlling its crystalline form (α/β ratio between 10/90 and 90/10) and particle morphology (non-spherical, microcrystalline) through specific processing conditions. This optimization allows mannitol to provide both excipient and lubricant functions with reduced lubricant quantities
2Reliability
If high quantities of lubricant are used in direct compression, then tablet ejection is improved, but taste and cost worsen
Solution Approach 1:
The patent optimizes mannitol crystalline parameters (α/β ratio) and particle characteristics to enhance lubricating efficiency. This allows reduction of lubricant quantity from conventional high levels to optimized lower levels, improving taste while maintaining adequate ejection
Solution Approach 2:
Mannitol serves multiple functions simultaneously: direct compression excipient, flow agent, and lubricant. This multi-functionality reduces or eliminates the need for separate lubricant additives, improving taste and reducing cost
3Ease of operation
If granular starch is used in coagglomerate with mannitol, then flow and compressibility are improved, but bacterial contamination and stability worsen
Solution Approach 1:
The patent completely removes granular starch from the composition, using mannitol alone as the direct compression excipient. This eliminates all harmful effects associated with starch (bacterial contamination, water sensitivity, stability issues) while maintaining satisfactory flow and compressibility through optimized mannitol characteristics
Solution Approach 2:
The patent replaces the problematic starch-mannitol coagglomerate system with a simpler, more stable mannitol-only system. This substitution eliminates the need for close control of manufacturing and storage required for starch-based systems
4Ease of operation
If granular starch is used in coagglomerate with mannitol, then flow and compressibility are improved, but water sensitivity and stability worsen
Solution Approach 1:
The patent extracts and eliminates granular starch from the formulation, relying solely on mannitol as the direct compression excipient. This removal eliminates water sensitivity and stability problems inherent to starch while maintaining compressibility through optimized mannitol crystal structure and particle morphology
Solution Approach 2:
The patent optimizes mannitol crystalline parameters (α/β ratio) and physical characteristics to enhance compressibility and flow without requiring starch. The controlled crystalline form provides stable, water-resistant properties while maintaining excellent compression characteristics
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 mannitol granules enable the production of tablets with low lubricant content, improved taste, and enhanced stability, while avoiding the drawbacks of granular starch, such as bacterial contamination and water sensitivity, and achieve satisfactory compressibility and flow without the need for high lubricant quantities.
Implementation Method 1
drying by atomization of the mannitol solution obtained in step (a) in a multiple-effect atomization tower
Implementation Method 2
non-spherical granules of microcrystalline mannitol, in which the mannitol is in both α crystalline form and β crystalline form
Data Source
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Figure 2
AI summary
The present invention relates to mannitol granules that are of use for the preparation of tablets by direct compression, which do not require a small amount of lubricant in order to be processed. The present invention also relates to a process for preparing such granules. The present invention also encompasses pulverulent compositions comprising these granules, and also direct compression processes using these pulverulent compositions. Finally, the present invention relates to tablets composed of these pulverulent compositions.