Donepezil Microspheres Sustained Release Parenteral Formulation
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Solution Overview
Problem
Current sustained-release formulations for donepezil, used to treat Alzheimer's disease, face challenges in maintaining effective drug concentration in the blood for an extended period and ensuring stable drug release, leading to low patient compliance and inefficiencies in oral administration.
Innovation Solution
Development of donepezil microspheres using biodegradable, biocompatible polymers like poly(lactide-co-glycolide) with a controlled release agent, such as xinofoate, napadisilate, or pamoate, to create a sustained-release parenteral formulation that maintains effective drug concentration for 2-12 weeks, optimizing drug loading and release rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If sustained-release microparticles of donepezil are prepared using copolymer of lactide and glycolide, then the drug can be released over time, but the content of donepezil in microparticles is only about 13.2% and the loading rate is only 66%, resulting in much drug loss and requiring too much administration amount for practical application
Solution Approach 1:
The patent changes the chemical parameters of the polymer system by using polycaprolactone instead of copolymer of lactide and glycolide, and adjusts the molecular weight and composition ratios to achieve both sustained release and high drug loading content simultaneously
Solution Approach 2:
The patent creates a composite microsphere system combining donepezil with polycaprolactone polymer matrix, optimizing the drug-polymer ratio to achieve high loading efficiency while maintaining controlled release properties over extended periods
2Ease of operation
If drugs are administered orally in tablet form, then the administration is simple, but it is difficult to orally administer anti-dementia drugs to patients suffering from the progression of dementia and drug compliance is low
Solution Approach 1:
The patent segments the drug delivery system into injectable microspheres that can be administered less frequently (every 2-12 weeks), transforming the oral tablet into a parenteral sustained-release formulation that bypasses the compliance issues of daily oral administration
Solution Approach 2:
The patent implements periodic administration intervals of 2-12 weeks through sustained-release microspheres, replacing frequent daily oral doses with less frequent injections that maintain effective drug concentrations throughout the interval
3Ease of operation
If sustained-release injections are used to reduce administration frequency, then convenience is improved, but it is difficult to make drugs be continuously and uniformly released while maintaining biological activities of drugs in the body for 4 weeks or more
Solution Approach 1:
The patent optimizes polymer parameters including molecular weight, composition ratio of polycaprolactone, and crosslinking degree to achieve uniform and continuous drug release over extended periods while maintaining drug biological activity
Solution Approach 2:
The patent performs preliminary optimization of the polymer matrix structure and drug distribution before administration, ensuring that the microspheres are pre-configured for uniform drug release throughout the sustained period
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 donepezil microspheres provide stable drug release for an extended period, improving patient compliance by maintaining effective blood concentrations and reducing the frequency of administration, while minimizing initial burst release through solvent washing.
Implementation Method 1
the content of donepezil is 15% by weight or more, the poorly soluble salt of donepezil is xinofoate, napadisilate or pamoate
Implementation Method 2
comprising donepezil or a pharmaceutically acceptable salt thereof, and a poorly soluble salt of donepezil as a controlled release agent
Implementation Method 3
a poorly soluble salt of donepezil as a controlled release agent, wherein the content of donepezil is 15% by weight or more, the poorly soluble salt of donepezil is xinofoate, napadisilate or pamoate
Data Source
Figure 1a~1b
Figure 1c~1d
Figure 1e~1f
AI summary
The present invention relates to a composition for parenteral administration, containing donepezil as an active ingredient, and a preparation method therefor. Donepezil, which has been conventionally used for oral or transdermal administration, is prepared as microparticles comprising a biodegradable and biocompatible polymer and a release controller so as to be provided as a pharmaceutical composition for sustained release parenteral administration, thereby enabling in vivo sustained release continuously for 2-12 weeks or more. Therefore, it is possible to reduce the frequency of administration to a patient and maintain an effective concentration in the blood for a long time.