Multiphasic Centanafadine Beads for High-Load Controlled Release
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Solution Overview
Problem
Developing a controlled-release pharmaceutical formulation for centanafadine, a BCS class 1 molecule with high solubility and permeability, is challenging due to its high therapeutic dose, particularly in bead form, necessitating a formulation that provides prolonged therapeutic efficacy with a high drug load.
Innovation Solution
A centanafadine multiphasic controlled-release pharmaceutical formulation is designed with a centanafadine continuous phase surrounding a centanafadine particulate phase, featuring burst, prolonged, and enteric release rates, allowing for a bi-phasic release of centanafadine in specific proportions and durations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If a controlled-release formulation is developed for centanafadine, then prolonged therapeutic efficacy is achieved, but the high therapeutic dose creates formulation challenges in bead form
Solution Approach 1:
The formulation is segmented into multiple bead types with different release characteristics (immediate-release beads, sustained-release beads, and enteric-coated beads). Each bead type contains centanafadine but releases the drug at different rates, allowing the high therapeutic dose to be distributed across multiple functional units rather than requiring a single complex bead formulation.
Solution Approach 2:
The formulation uses composite bead structures combining different materials and release mechanisms. Sustained-release beads utilize polymer matrices or coating layers that control drug release kinetics, while enteric-coated beads combine pH-sensitive coatings with drug payloads. This composite approach enables prolonged therapeutic efficacy by integrating multiple release profiles in one formulation system.
2Quantity of substance
If a high drug load is incorporated in the formulation, then the therapeutic dose is achieved, but the controlled-release mechanism becomes more difficult to implement
Solution Approach 1:
The high drug load is segmented across multiple bead types rather than concentrated in a single bead formulation. Each bead type (immediate-release, sustained-release, enteric-coated) contains a manageable amount of centanafadine, making manufacturing easier while the combined effect of all beads achieves the required high therapeutic dose.
Solution Approach 2:
The formulation varies physical parameters such as bead size, coating thickness, and polymer composition across different bead types to optimize drug release while maintaining manufacturability. By adjusting these parameters rather than increasing drug concentration uniformly, the formulation achieves high overall drug load without compromising the controlled-release mechanism or manufacturing ease.
3Duration of action of moving object
If multiple release rates are incorporated in the formulation, then prolonged therapeutic efficacy is achieved, but the formulation structure becomes more complex
Solution Approach 1:
Instead of creating a single complex multi-layered bead with multiple release rates, the formulation segments different release mechanisms into separate bead types. Immediate-release beads provide rapid initial therapy, sustained-release beads provide extended delivery, and enteric-coated beads provide pH-dependent release. This segmentation achieves prolonged therapeutic efficacy while keeping each individual bead type structurally simple and easier to manufacture than a single integrated multi-rate bead.
Data Source
AI summary
A centanafadine multiphasic controlled-release pharmaceutical formulation comprising a centanafadine continuous phase surrounding a centanafadine particulate phase, wherein the amount of centanafadine contained in the centanafadine continuous phase facilitates a first release rate of the centanafadine, and the amount of centanafadine contained in the centanafadine particulate phase facilitates the second and/or third release rate of the centanafadine. The centanafadine particulate phase is formulated in the form of a plurality of the centanafadine particulates and the centanafadine continues phase is formulated in the form of centanafadine burst release coat surrounding one or more centanafadine particulates of the plurality of the centanafadine particulates. The related method of making the pharmaceutical formulation, and treatment of the disease conditions using the centanafadine multiphasic controlled-release pharmaceutical formulation is also disclosed herein.