Mannitol-Starch Coagglomerates for Orodispersible Tablet Hardness
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Solution Overview
Problem
Current pharmaceutical excipients, such as mannitol and starch, face challenges in achieving optimal hardness, disintegration properties, and flowability in orodispersible tablets, with existing solutions either being expensive, hygroscopic, or requiring additional disintegrating agents that compromise stability.
Innovation Solution
A coagglomerate of fine-grained mannitol and granular starch, specifically with a beta-form mannitol and a mannitol/starch ratio between 90/10 and 50/50, is used to create tablets with improved hardness and rapid disintegration, leveraging the coagglomerate's binding and disintegrating properties through direct compression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If starch is used as a diluent and binder in orodispersible tablets, then good disintegrating properties are achieved, but the tablets exhibit poor flowability and compressibility due to small particle size and low density
Solution Approach 1:
The patent combines starch with mannitol particles to create a composite excipient system. The mannitol particles (50-200 μm) serve as a carrier that improves flowability and compressibility, while the starch (10-50 μm) provides disintegrating properties. This merging allows the mixture to exhibit both good manufacturing characteristics and effective disintegration in the mouth.
2Ease of manufacture
If microcrystalline cellulose is used as a direct compression excipient, then satisfactory flow and compressibility are achieved, but tablet hardness reduces after water uptake during storage and an unpleasant suffocation sensation occurs
Solution Approach 1:
The patent replaces microcrystalline cellulose with a starch-mannitol mixture that avoids the long-term stability and sensory issues. While starch alone has poor flowability, the combination with mannitol creates a system that provides adequate compressibility without the hygroscopicity problems of MCC, maintaining tablet integrity and pleasant oral sensation.
3Ease of manufacture
If atomized lactose is used to improve compressibility, then satisfactory flow properties are achieved, but stability decreases and shelf life is shortened
Solution Approach 1:
The patent uses crystallized lactose instead of atomized lactose. Crystallized lactose offers superior stability and shelf life compared to atomized forms, while the addition of mannitol particles provides the necessary compressibility and flowability improvements that would otherwise require atomization.
4Duration of action of moving object
If multiple excipients including super disintegrating agents and effervescent agents are added to improve disintegration time, then rapid dissolution is achieved, but formulation complexity and cost increase
Solution Approach 1:
The patent creates a multi-functional excipient system where the starch-mannitol mixture serves multiple purposes: starch provides disintegration through swelling, mannitol provides structure and rapid dissolution, and the combination eliminates the need for separate super disintegrating agents and effervescent agents. This universal approach simplifies the formulation while achieving rapid disintegration.
5Strength
If fine-grained mannitol is used to improve tablet hardness, then compressive strength increases, but flowability deteriorates due to small particle size
Solution Approach 1:
The patent merges fine-grained mannitol (providing hardness) with starch particles (providing flowability assistance). The starch acts as a flow promoter that compensates for the poor flow characteristics of fine mannitol, while the mannitol ensures adequate compressive strength and tablet hardness. This synergistic combination resolves the trade-off between hardness and flowability.
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 coagglomerate enables the production of orodispersible tablets that disintegrate within 1.5 minutes, maintaining hardness between 100 N and 110 N, and exhibits suitable viscosity and compressive behavior, overcoming previous issues of friability and flowability.
Implementation Method 1
direct compression
Implementation Method 2
cohesion after compaction of the particles which determines the hardness of the tablets
Implementation Method 3
Starch has good disintegrating properties due to its swelling power in water
Implementation Method 4
the ability to flow in manufacturing devices: regular supply of the compression chamber
Data Source
AI summary
The subject of the invention is coagglomerates of mannitol, the laser volume-average diameter D4,3 of which is between 1 and 200 µm, and of granular starch, characterized in that they have a disintegration behaviour determined according to a test A such that the relaxation time measured is between 30 and 100 seconds and the swelling force is between 0.8 and 3.0 N.