Lurasidone Microsphere Formulations for Stable Plasma Release
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Solution Overview
Problem
Current oral administration of lurasidone for treating schizophrenia and depression in bipolar disorder leads to withdrawal symptoms due to fluctuating plasma drug concentrations, and existing microsphere formulations like Risperdal® Consta® cause side effects and require alternative treatment options.
Innovation Solution
Development of microsphere formulations with lurasidone encapsulated in biodegradable polymers, specifically poly(D,L-lactide-co-glycolide), achieving a high drug load, small particle size, and low initial burst release, with sterilization by irradiation, for extended release over 30 or 60 days via intra-articular, intramuscular, or subcutaneous injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oral administration of lurasidone is used, then the drug can be easily administered, but withdrawal symptoms occur due to fluctuating plasma concentrations
Solution Approach 1:
The patent divides the drug delivery system into multiple microsphere particles that are injected and distributed throughout the body, with each microsphere acting as an independent release unit. This segmentation allows for sustained release over time, preventing the sharp peaks and troughs associated with oral dosing while maintaining ease of administration through simple injection.
Solution Approach 2:
The patent employs dynamic release characteristics where the microsphere formulation provides initial rapid release followed by sustained release over time. The release profile is designed to be time-dependent, transitioning from burst release to controlled sustained release, thereby maintaining stable plasma concentrations while preserving ease of administration.
2Duration of action of moving object
If existing microsphere formulations like Risperdal Consta are used, then extended release is achieved, but side effects occur and patient compliance is reduced
Solution Approach 1:
The patent modifies critical parameters of the microsphere formulation including polymer composition (using PLGA 75:25), molecular weight, particle size distribution, and drug:polymer ratio to optimize the release profile. These parameter changes enable extended release duration while minimizing side effects by providing more controlled and stable drug concentrations compared to existing formulations.
Solution Approach 2:
The patent uses composite microsphere structures combining specific polymer ratios (PLGA 75:25) with lurasidone drug molecules. This composite approach creates a formulation that maintains extended release capability while improving biocompatibility and reducing side effects through optimized material composition.
3Quantity of substance
If high drug load is achieved, then therapeutic effectiveness is improved, but initial burst release increases
Solution Approach 1:
The patent applies preliminary coating and surface modification techniques to the microsphere particles before drug incorporation. This preliminary action creates a protective barrier that controls the release of lurasidone, enabling high drug load while preventing excessive initial burst release by modulating the surface properties and diffusion characteristics of the microspheres.
4Ease of operation
If small particle size is used, then injection feasibility is improved, but manufacturing precision becomes more difficult
Solution Approach 1:
The patent replaces traditional mechanical mixing and filtration methods with advanced homogenization techniques and controlled emulsification processes. This substitution enables precise control of microsphere particle size at the nanoscale while maintaining injection feasibility, overcoming the manufacturing precision challenges associated with small particle sizes.
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 microsphere formulations provide sustained release of lurasidone with reduced initial burst, maintaining therapeutic levels for extended periods, improving patient compliance and minimizing side effects, while allowing for less frequent dosing.
Implementation Method 1
a biodegradable polymer, wherein each polymer microsphere comprises a drug load of lurasidone of greater than 55% by weight of the polymer microsphere
Implementation Method 2
The microsphere formulations provide sustained release of lurasidone with reduced initial burst
Implementation Method 3
the microsphere formulations are sterilized by irradiation
Data Source
AI summary
Extended-release microsphere formulations comprising lurasidone are provided. In one aspect. the microsphere formulations are characterized in that the lurasidone is released in vivo in humans over a period of about 30 days or about 60 days. Methods for making and using the formulations are also provided.