Orally Disintegrating Tablet Hardness via Multi-Stage Granulation
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Solution Overview
Problem
Conventional disintegrative particulate compositions and orally-disintegrating tablets face challenges in achieving a balance between tablet hardness and disintegrability, particularly when crystalline cellulose is added, which increases hardness but prolongs disintegration time.
Innovation Solution
A method involving a multi-stage granulation process using a first and second wet granulation step with specific combinations of acid-type carboxymethylcellulose, other disintegrator components, and excipients, including crystalline cellulose, to produce a disintegrative particulate composition that enhances tablet hardness and disintegrability while maintaining low compression forces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If molding pressure is increased to increase tablet hardness, then tablet hardness is improved, but disintegration time is prolonged
Solution Approach 1:
The patent divides the granulation process into multiple stages (first wet granulation step, second wet granulation step, and drying step) to create particulate compositions with optimized internal structure. This segmentation allows different functional components to be incorporated at different stages, achieving both hardness and disintegrability without requiring high molding pressure
Solution Approach 2:
The patent changes the physical and chemical parameters of the granulation process, including the order of adding components (acid-type carboxymethylcellulose added in second wet granulation step), moisture content control, and drying conditions. These parameter changes create particles with optimized pore structure and density that achieve superior moldability and disintegrability simultaneously
2Loss of time
If molding pressure is reduced to shorten disintegration time, then disintegration time is improved, but tablet hardness decreases
Solution Approach 1:
The patent performs preliminary actions during the multi-stage granulation process to pre-establish the desired tablet properties. Acid-type carboxnymethylcellulose is added and processed in advance during the second wet granulation step to create a particle structure that will naturally provide both hardness and rapid disintegration upon compression, eliminating the need for high molding pressure
Solution Approach 2:
The patent creates composite particulate compositions by combining multiple components (excipients, disintegrators, acid-type carboxnymethylcellulose) with different functional properties. The composite structure achieved through multi-stage granulation provides synergistic effects where the combination of materials delivers both superior hardness and rapid disintegration at lower compression forces
3Strength
If crystalline cellulose is added to increase tablet hardness, then tablet hardness is improved, but disintegration time is prolonged
Solution Approach 1:
The patent extracts or removes the problematic effect of crystalline cellulose by adding acid-type carboxnymethylcellulose in a specific sequence during the second wet granulation step. This taking out approach isolates the hardness-providing function from the disintegration-inhibiting effect, allowing crystalline cellulose to contribute to hardness while the acid-type carboxnymethylcellulose ensures rapid disintegration
Solution Approach 2:
The patent applies local quality by creating regions within the particulate composition with different functional characteristics. The multi-stage granulation process creates particles with heterogeneous internal structure where certain regions provide hardness (from crystalline cellulose) while other regions provide disintegration functionality (from acid-type carboxnymethylcellulose added in specific proportions and sequences)
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 method results in orally-disintegrating tablets with superior hardness and disintegrability, achieving higher tablet hardness with shorter disintegration times even with the addition of crystalline cellulose, providing excellent moldability and production efficiency.
Implementation Method 1
an acid-type carboxymethylcellulose is a cellulose derivative otherwise called 'carmellose', and this substance has properties that, when water is added to the substance, the substance swells
Implementation Method 2
A method involving a multi-stage granulation process using a first and second wet granulation step
Data Source
AI summary
The present application provides an orally-disintegrating tablet having excellent tablet hardness and disintegrability. The present application further provides a method of producing a disintegrative particulate composition including three components consisting of a first disintegrator component of an acid-type carboxymethylcellulose, a second disintegrator component and an excipient. The method includes a first wet granulation step using any two of the three components, and a second wet granulation step using granules obtained in the first wet granulation step and the remaining one component of the three components not used in the first wet granulation step. The production method may further includes a crystalline cellulose as a fourth component or a third step of mixing a crystalline cellulose into granules obtained in the second wet granulation step. Disintegrative particulate compositions obtained by these methods are also disclosed.