3D-Printed Droxidopa Tablets for High-Load Rapid Disintegration
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing droxidopa dosage forms, particularly tablets and capsules, are difficult for certain patients to self-administer, especially those with swallowing difficulties, and are prone to color change due to environmental factors, with limited capacity and rapid disintegration issues.
Innovation Solution
Development of rapidly-orodispersible tablets using three-dimensional printing (3DP) with a porous, bound matrix containing up to 300 mg of droxidopa, stabilized by an acidulant like citric acid, and a binder, which disintegrates within 30 seconds in saliva, and includes a functional seam for easy division.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional compressed-tableting techniques are used to create orodispersible tablets, then the tablets can be made to disintegrate rapidly, but the mass of active pharmaceutical ingredient (droxidopa) that can be contained within a single tablet is limited
Solution Approach 1:
The patent transitions from conventional two-dimensional compressed tablets to three-dimensional printed tablets with porous internal structures. The 3DP process creates a three-dimensional matrix that maintains structural integrity while allowing rapid fluid penetration, enabling higher droxidopa content (up to 300 mg) while preserving rapid disintegration capability through controlled porosity and internal architecture rather than relying solely on traditional compression mechanisms.
Solution Approach 2:
The patent employs porous materials as a core structural element in the 3DP tablets. The porous internal structure provides high surface area to volume ratio, allowing rapid penetration of saliva and other fluids throughout the tablet matrix. This porosity enables the tablet to disintegrate rapidly even while containing higher masses of droxidopa, resolving the contradiction between quantity of substance and ease of operation.
2Quantity of substance
If compressed tablets are made with higher droxidopa content, then the dosage strength increases, but the tablets become less rapidly orodispersible
Solution Approach 1:
The patent applies local quality by creating regions of different density and porosity within the tablet structure. The 3DP process allows for spatially varying properties where certain areas are more porous to facilitate rapid fluid penetration, while other areas provide structural support and maintain droxidopa content. This localized variation in material properties enables high droxidopa content while maintaining rapid disintegration speed.
Solution Approach 2:
The patent utilizes parameter changes in the 3DP manufacturing process to control tablet properties. By adjusting parameters such as layer thickness, binder concentration, infill density, and material composition during printing, the process creates tablets with optimized porosity and structural characteristics that maintain rapid disintegration even at higher droxidopa concentrations, decoupling the relationship between dosage strength and disintegration speed.
3Stability of the object's composition
If droxidopa tablets are stored in sealed bottles with desiccants to prevent color change, then stability improves, but the complexity of storage requirements increases
Solution Approach 1:
The patent applies preliminary action by incorporating stabilizing agents and antioxidants directly into the tablet formulation during manufacturing. The 3DP process allows for precise incorporation of protective agents that prevent oxidation and color change before the tablet is even administered. This preliminary stabilization eliminates the need for complex storage conditions with desiccants and sealed bottles, as the tablet is inherently protected against environmental factors.
Solution Approach 2:
The patent introduces intermediary substances such as antioxidants and stabilizing agents that act as mediators between the droxidopa and harmful environmental factors. These intermediaries prevent direct contact between droxidopa and oxidizing agents, moisture, or light that would cause color change. By incorporating these protective intermediaries into the tablet matrix during 3DP manufacturing, the patent achieves color stability without requiring complex external storage systems.
4Speed
If the tablet periphery disintegrates first in compressed ODT, then rapid disintegration is achieved, but the tablet interior becomes shielded from solvent increasing disintegration time
Solution Approach 1:
The patent employs porous materials with controlled pore sizes and distributions that allow simultaneous penetration of fluids throughout the entire tablet matrix. The porous structure ensures that solvent can reach both the periphery and interior of the tablet at the same time, eliminating the shielding effect that occurs in conventional compressed tablets. This results in uniform and rapid disintegration across the entire tablet structure.
Solution Approach 2:
The patent transitions from the periphery-first disintegration mechanism of conventional two-dimensional compressed tablets to a three-dimensional simultaneous disintegration approach. The 3DP process creates a three-dimensional porous matrix where fluid penetration occurs from multiple directions simultaneously, reaching the interior and periphery at the same time. This dimensional change in the disintegration mechanism ensures uniform composition breakdown without the shielding problem of traditional tablets.
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 3DP tablets provide easy self-administration, resistance to color change, and maintain high droxidopa content while ensuring rapid disintegration and stability under varying conditions.
Implementation Method 1
stabilized by an acidulant like citric acid
Implementation Method 2
a binder, which disintegrates within 30 seconds in saliva
Implementation Method 3
disintegrates within 30 seconds in saliva
Data Source
AI summary
A rapidly-orodispersible tablet containing a porous, bound powder matrix containing droxidopa. The bound matrix contains an acidulant, particularly citric acid, to delay, reduce, or inhibit the coloration of droxidopa during stress storage conditions, and suppress the effect of glycerin on the coloration of droxidopa-containing tablets. The tablet can be dividable along a functional seam printed into the bound powder matrix, to divide the tablet into sub-dosage units of the same mass of droxidopa.