Lurasidone Depot Formulation Syringeability via Particle Segmentation
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Solution Overview
Problem
Developing a depot formulation of lurasidone that provides a therapeutic dose over an extended period while maintaining stability and syringeability, especially for low-solubility drugs like lurasidone, is challenging due to high concentrations and particle size requirements, and existing solutions often necessitate surfactants and larger needle sizes.
Innovation Solution
A depot formulation of lurasidone with a mean particle size of 4 μm to 100 μm, using a suspending agent and buffer, suitable for injection via 20-gauge or smaller needles, which does not require surfactants and maintains stability and syringeability, allowing for delivery of a therapeutic dose for at least 28 days.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If high concentrations of lurasidone are used to provide therapeutic levels over an extended period, then the duration of action is improved, but the syringeability and ease of administration deteriorate
Solution Approach 1:
The formulation segments the high concentration drug into suspended particles rather than a dissolved solution, allowing high drug content while maintaining injectability through particle suspension in a vehicle
Solution Approach 2:
The patent changes the physical state parameter from dissolved to suspended particles, and optimizes particle size distribution to achieve both high concentration (≥250 mg/mL) and good syringeability through the needle
2Ease of operation
If small particle sizes are used to improve syringeability, then the ease of operation is improved, but the stability and risk of agglomeration deteriorate
Solution Approach 1:
The formulation uses a composite system combining lurasidone particles with a specific vehicle containing suspending agents (such as polysorbate 80 and polyethylene glycol 4000) that prevent agglomeration while maintaining small particle size for syringeability
Solution Approach 2:
The suspending agents in the vehicle act as intermediaries between the drug particles and the injection medium, preventing particle agglomeration and maintaining stable suspension during storage and administration
3Productivity
If large needle sizes are used to administer high concentration formulations, then the productivity and ease of administration are improved, but the patient comfort and compliance deteriorate
Solution Approach 1:
The patent changes the particle size distribution parameters to optimize flow characteristics, enabling high concentration formulations to pass through smaller gauge needles (20 gauge or smaller) without compromising administration efficiency or causing excessive patient discomfort
4Duration of action of moving object
If extended release is achieved through high drug concentration, then the duration of action is improved, but the manufacturing complexity and formulation development difficulty worsen
Solution Approach 1:
The formulation segments the drug into particles of controlled size distribution that naturally provide extended release through dissolution over time, avoiding the need for complex controlled-release mechanisms or multiple formulation components
Solution Approach 2:
The particle suspension formulation uses the natural dissolution and release characteristics of the suspended particles to achieve extended release, eliminating the need for complex release-control mechanisms or additional formulation complexity
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 formulation achieves stable and consistent extended release of lurasidone over 28 days with improved syringeability, even for high doses, using smaller needles, enhancing patient compliance and comfort.
Implementation Method 1
A depot formulation of lurasidone with a mean particle size of 4 μm to 100 μm, using a suspending agent and buffer
Data Source
AI summary
The present disclosure relates generally to depot formulations of lurasidone and methods of making depot formulations of lurasidone. The depot formulations include a suspending agent and are highly syringeable.