Bedaquiline Micro- and Nanoparticle Sustained Release Formulations
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current tuberculosis drugs, including bedaquiline, face challenges in pharmacokinetic properties that make them unsuitable for long-acting formulations, and existing models lack reliability for pharmacodynamic assessment, leading to high pill burdens and potential resistance due to frequent dosing requirements.
Innovation Solution
Development of micro- or nanoparticle formulations of bedaquiline as a suspension for intramuscular or subcutaneous injection, with a surface modifier adsorbed onto the particles, allowing for intermittent administration at extended intervals (e.g., one week to two years) to maintain effective plasma levels for treating and preventing mycobacterial infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bedaquiline is administered frequently to maintain effective plasma levels, then treatment effectiveness is improved, but pill burden increases and patient compliance decreases
Solution Approach 1:
The patent segments the drug delivery system into micro- or nanoparticle formulations that can be administered via injection rather than oral tablets. This segmentation transforms the dosage form from multiple daily pills to a single injectable formulation, reducing pill burden while maintaining treatment effectiveness through sustained release from the particle system.
Solution Approach 2:
The micro- or nanoparticle formulations are designed to pre-load and store bedaquiline within their structure, creating a reservoir that releases the drug over time. This preliminary action of drug loading into particles allows for extended plasma level maintenance without requiring frequent re-administration, thereby improving compliance.
2Reliability
If bedaquiline is administered frequently to maintain effective plasma levels, then treatment effectiveness is improved, but the number of dosage forms increases
Solution Approach 1:
The micro- or nanoparticle formulations provide continuous drug release over an extended period, maintaining effective plasma levels of bedaquiline without interruption. This continuous action from a single dosage form eliminates the need for multiple daily administrations, thereby reducing pill burden while preserving treatment effectiveness.
Solution Approach 2:
The particle formulations are pre-loaded with sufficient bedaquiline to sustain therapeutic levels throughout the dosing interval. This preliminary drug loading into the particle matrix allows a single dosage form to replace multiple individual pills, reducing the quantity of substance the patient must handle while maintaining effective concentrations.
3Reliability
If bedaquiline is administered frequently, then plasma levels are maintained above minimum level, but risk of resistance emergence increases
Solution Approach 1:
The micro- or nanoparticle formulations ensure continuous maintenance of bedaquiline plasma levels above the minimum inhibitory concentration throughout the dosing interval. This uninterrupted therapeutic pressure prevents bacterial adaptation and resistance emergence, achieving the same protective effect as frequent dosing but with a single administration.
4Ease of operation
If micro- or nanoparticle formulations are used for sustained release, then administration frequency is reduced, but formulation complexity increases
Solution Approach 1:
The patent utilizes parameter changes in the particle system, specifically controlling particle size (micro- or nanometer scale) and surface properties to achieve sustained drug release. By adjusting these physical parameters of the formulation, the system provides extended release kinetics that reduce administration frequency without requiring complex delivery mechanisms or active control systems.
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 micro- or nanoparticle formulations of bedaquiline provide sustained release, reducing the frequency of administrations, improving patient compliance, and maintaining effective plasma levels for prolonged periods, thereby effectively treating and preventing mycobacterial infections with a lower pill burden and minimizing resistance.
Implementation Method 1
micro- or nanoparticles comprising: (a) bedaquiline, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier; and (b) a pharmaceutically acceptable aqueous carrier
Data Source
AI summary
This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the anti-TB compound bedaquiline, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of a pathogenic mycobacterial infection.