Donepezil Sustained-Release Microspheres Using Polylactide
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Solution Overview
Problem
Current donepezil formulations for dementia treatment face challenges such as low drug content, poor injectability, and non-uniform particle size, leading to inadequate sustained release and administration difficulties.
Innovation Solution
Development of sustained-release microsphere injections containing at least 20% donepezil using polylactide with a lactide ratio of 100% and intrinsic viscosity of 0.16 to 0.75 dL/g, ensuring uniform particle size and improved injectability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If copolymers of lactide and glycolide are used to produce donepezil-containing microspheres, then the microspheres can be produced, but the donepezil content is low (13.2%) requiring very large administered doses
Solution Approach 1:
The patent changes the polymer composition parameter from copolymers to homopolymer (polylactide with 100% lactide ratio), and optimizes the intrinsic viscosity parameter to 0.16 to 0.75 dL/g. This parameter optimization enables achieving at least 20% donepezil content while maintaining manufacturability and injectability, resolving the contradiction between drug content and administered dose volume.
2Quantity of substance
If high viscosity biodegradable polymer is used to increase drug content, then drug content increases (36.1%), but particle nonuniformity causes clogging and difficulty in administration
Solution Approach 1:
The patent optimizes the intrinsic viscosity parameter to a specific range (0.16 to 0.75 dL/g) and specifies polylactide with 100% lactide ratio, avoiding both too-low and too-high viscosity extremes. This parameter optimization achieves at least 20% drug content while maintaining particle uniformity and injectability, resolving the contradiction between drug content and particle uniformity.
3Quantity of substance
If high viscosity polymer is used to achieve high drug content, then drug content increases, but it becomes difficult to maintain reproducibility in commercial production
Solution Approach 1:
The patent defines a specific intrinsic viscosity range (0.16 to 0.75 dL/g) and 100% lactide ratio for polylactide, providing clear manufacturing specifications. This parameter standardization enables consistent reproduction of microspheres with at least 20% drug content across commercial production, resolving the contradiction between drug content and reproducibility.
4Duration of action of moving object
If insoluble salt is used as release control agent, then sustained release is achieved, but the manufacturing process becomes too complicated and safety data is required
Solution Approach 1:
The patent removes the insoluble salt release control agent from the formulation, relying instead on the controlled degradation of polylactide polymer matrix to achieve sustained release. This extraction of the complex release control agent simplifies the manufacturing process while maintaining at least 20% drug content and sustained release characteristics, resolving the contradiction between sustained release and manufacturing 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 solution achieves stable and prolonged drug release, enhancing patient compliance and therapeutic effectiveness with improved injectability and uniformity.
Implementation Method 1
biodegradable microsphere injection preparation
Data Source
AI summary
The present invention relates to a sustained-release injectable preparation comprising biodegradable polymer microspheres containing donepezil as an active ingredient, and a method for producing the same, and a sustained-release preparation of donepezil sustained-release microspheres having a high content of donepezil and a method for producing the same. It is possible to maximize the therapeutic effect by decreasing gastrointestinal side effects frequently encountered in conventional oral administration agents and increasing patients' compliance of medicines.