3D Printed Core-Shell Dosage Form for Zero-Order Release
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Solution Overview
Problem
Current diffusion-controlled dosage forms require multi-step manufacturing processes and struggle to achieve a zero-order release profile, with porosity and macroscopic defects hindering precise control over API release, especially for highly water-soluble APIs.
Innovation Solution
A core-and-shell dosage form is developed using three-dimensional printing, where the shell is made from a release-blocking polymer combined with a release-regulating polymer, potentially containing a plasticizer, to create a continuous, defect-free barrier that controls API release through diffusion, allowing for adjustment of the release profile by varying the polymer proportions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional multi-step manufacturing processes are used to create diffusion-controlled dosage forms, then the release barrier can be applied, but the manufacturing complexity increases and manufacturing precision decreases due to potential defects
Solution Approach 1:
The patent combines the core and shell manufacturing into a single three-dimensional printing process, eliminating the need for separate coating steps. The 3DP process deposits powder layer-by-layer and binds it with liquid binder, creating both the structural core and the release-controlling shell in one continuous operation, thereby reducing manufacturing complexity while maintaining defect-free barriers.
Solution Approach 2:
The patent controls the release profile by adjusting the composition and thickness of the shell, which are parameters that can be precisely controlled during the 3DP process. By varying the shell thickness and material composition, the diffusion characteristics of the API release can be tuned without requiring additional manufacturing steps.
2Manufacturing precision
If a thin release barrier is used to control diffusion, then the API release can be controlled, but the barrier is more prone to macroscopic defects
Solution Approach 1:
The patent applies different properties to different regions of the dosage form. The shell region is designed with specific material composition and controlled thickness to provide diffusion control, while the core region contains the API. The 3DP process allows precise local control of shell thickness and composition, ensuring adequate barrier integrity while maintaining diffusion control functionality.
3Manufacturing precision
If multiple manufacturing processes are used for core and shell, then each component can be optimized, but the overall manufacturing time increases
Solution Approach 1:
The patent merges the manufacturing of the core and shell into a single 3DP process operation. Both components are created simultaneously in one build cycle, eliminating the sequential steps of core formation followed by shell coating. This significantly reduces manufacturing cycle time while the 3DP process maintains precision through layer-by-layer controlled deposition.
4Manufacturing precision
If a defect-free shell is required for diffusion control, then the release profile precision improves, but the manufacturing difficulty increases
Solution Approach 1:
The 3DP process inherently creates defect-free shells through its layer-by-layer deposition mechanism. Each layer is deposited and bound in place, self-correcting potential defects that would occur in traditional coating methods. The process automatically ensures uniform thickness and continuous coverage without requiring post-manufacturing inspection or repair steps.
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
This approach enables the production of dosage forms with a nearly zero-order release profile, maintaining structural integrity and precise control over API release, even for highly water-soluble APIs, while simplifying the manufacturing process to a single-step 3DP method.
Implementation Method 1
The release-regulating polymer may be such that upon exposure to water, path 280 attains a state such that water and aqueous API solution can diffuse along that path through the shell 120.
Implementation Method 2
When the fluid seeping into the core encounters API, the fluid may dissolve API to form an aqueous API-containing solution in the core region of the dosage form.
Implementation Method 3
The dissolved API has then diffused outward through the release barrier into the patient's digestive system.
Data Source
AI summary
The invention includes a core-and-shell dosage form or unit in which the core contains API and in which the shell substantially governs the release such as by controlling diffusion of API through the shell. The shell may comprise a release-blocking polymer, and particles of a release-regulating polymer. The shell may be substantially impervious but the release-regulating polymer may become suitable to allow diffusion through it when activated. The core may include a buffer region between the shell and the API-containing portion of the core. The dosage form may include multiple units. The dosage form of the invention is capable of providing a release profile whose time scale can be adjusted by adjusting powder composition, and which may be approximately zero-order release. The invention further includes methods of manufacturing such a dosage form, such as three-dimensional printing.