3D Printed Amorphous Solid Dosage Forms Without Recrystallization
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Solution Overview
Problem
Existing 3D printing processes for solid pharmaceutical administration forms face challenges such as poor solubility, recrystallization, impaired content uniformity, and mechanical instability of active ingredients, particularly when using amorphous forms, limiting their applicability and effectiveness.
Innovation Solution
A 3D printing process involving a drop-on-powder technique with jet printing of a binding medium onto a powder bed to create amorphous solid dispersions in a polymeric matrix, allowing precise control over particle fusion and structure formation, using a 3D printer with horizontal X-Y axes and a jet head, enabling the production of high-content, fast-disintegrating dosage forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If FDM or FFF process is used to manufacture pharmaceutical dosage forms, then continuous filament production and layer-by-layer printing are achieved, but recrystallization of active ingredient occurs during heating and high drug loads impair mechanical properties
Solution Approach 1:
A binder jetting process is introduced as an intermediary step between powder preparation and final dosage form creation. The liquid binder acts as a mediator that selectively binds powder particles without requiring extensive heating that would cause recrystallization, thus preserving the amorphous state while enabling dosage form construction.
Solution Approach 2:
The process changes the thermal parameters by avoiding the high temperatures required in FDM/FFF processes. Instead of heating to melt filaments, the binder jetting process uses ambient or mildly elevated temperatures with liquid binding agents, preventing the thermal conditions that trigger recrystallization of the active ingredient.
2Productivity
If DPE process is used to avoid double heating, then manufacturing steps are reduced, but de-mixing of powder components occurs during printing leading to impaired content uniformity
Solution Approach 1:
The manufacturing process is segmented into distinct steps: powder preparation with uniform mixing, followed by binder jetting where liquid binder is selectively deposited. This segmentation allows the powder blend to maintain its uniformity during the binding process, preventing de-mixing while still achieving efficient manufacturing through the direct printing approach.
Solution Approach 2:
The mechanical extrusion and melting system of DPE is replaced with a liquid deposition system. Instead of mechanically forcing powder through a heated nozzle where de-mixing occurs, the process uses a jet printing system that deposits liquid binder onto the powder bed, allowing powder components to remain in place and maintain uniform distribution.
3Shape
If SLS process is used to produce porous dosage forms, then laser amorphization is achieved, but very high temperatures at certain points have detrimental effect on API stability
Solution Approach 1:
A liquid binder serves as an intermediary that enables porous structure formation without requiring laser-induced high temperatures. The binder jetting process creates porosity through selective binding and controlled drying, eliminating the need for laser heating that would otherwise be required to achieve similar porous structures while protecting the API from thermal degradation.
Solution Approach 2:
The laser-based thermal system is replaced with a liquid deposition and evaporation system. Instead of using focused laser energy to sinter particles and create pores, the process uses liquid binder deposition followed by controlled drying, achieving porous structure formation through phase change of the binder rather than thermal sintering, thus avoiding temperatures that would harm API stability.
4Reliability
If amorphous solid dispersion is used to increase dissolution rates, then oral bioavailability is improved, but manufacturing difficulty increases due to short transition times in hot end
Solution Approach 1:
The amorphous solid dispersion is prepared in advance as pre-formed powder particles before the binder jetting process. This preliminary preparation allows the amorphous material to be handled in a stable powder form during printing, eliminating the need for short, high-speed transition times in a hot end that would be required if amorphization had to occur during the printing process itself.
Solution Approach 2:
The hot melt extrusion system required for real-time amorphization during printing is replaced with a binder jetting system that works with pre-prepared amorphous powder. Instead of using thermal energy to maintain the amorphous state during extrusion, the process uses liquid binding agents that can be applied to amorphous powder at ambient or mildly elevated temperatures, greatly simplifying the manufacturing process.
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 process achieves high-content, amorphous solid dosage forms with enhanced solubility and bioavailability, overcoming limitations of existing methods by ensuring uniformity and mechanical stability, suitable for immediate release formulations.
Implementation Method 1
jet printing a liquid material onto the powder whereby the liquid material provides binding of the powder
Implementation Method 2
the active ingredient is present as an amorphous solid dispersion in a polymeric matrix... compounds exhibit higher dissolution rates when compared to their crystalline state
Data Source
AI summary
The present invention relates to a process for the preparation of a solid pharmaceutical administration form comprising an amorphous solid dispersion using a 3D printing process. The process is a printing process that allows the production of a solid pharmaceutical solid administration form comprising an amorphous solid dispersion in an easy and flexible manner and the possibility to achieve fast disintegrating dosage forms with high drug loads.