Donepezil Liquid Injectable Composition with PLGA Polymer
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Solution Overview
Problem
Current treatments for Alzheimer's disease, schizophrenia, Parkinson's disease, and Down Syndrome using donepezil lack effective controlled release formulations that are free from polyethylene glycols and microspheres, and do not provide a suitable therapeutic index with low adverse reactions.
Innovation Solution
A liquid injectable composition comprising a bioerodible and biodegradable release retardant polymer (PLGA or PLA) and a biocompatible solvent (such as N-methyl pyrrolidone) with donepezil, forming a controlled release depot upon administration, which can be administered intramuscularly or subcutaneously.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If polymeric controlled release additives (PLGA/PLA) are used to form controlled release implant, then duration of action is improved, but device complexity increases
Solution Approach 1:
The patent combines donepezil with PLGA/PLA polymers in a single injectable composition that forms a controlled release implant in situ, merging the drug delivery function with the polymer matrix structure to achieve sustained release without complex external devices
Solution Approach 2:
The patent adjusts the polymer-to-drug ratio and polymer molecular weight parameters in the injectable composition to control the degradation rate and release profile of donepezil, optimizing duration of action through compositional parameter modification
2Ease of manufacture
If polyethylene glycols are included in polymeric compositions, then ease of manufacture is improved, but harmful factors increase due to adverse reactions
Solution Approach 1:
The patent removes polyethylene glycol from the polymeric composition while retaining PLGA/PLA polymers as the sole polymer component, eliminating the harmful adverse reactions associated with PEG while maintaining controlled release functionality
Solution Approach 2:
The patent uses PLGA/PLA polymers as biocompatible and biodegradable materials that provide both ease of manufacture through established protocols and reduced harmful effects due to their favorable safety profile compared to PEG-containing formulations
3Ease of operation
If donepezil is administered in conventional formulations, then ease of operation is improved, but therapeutic index deteriorates due to high burst effect and adverse reactions
Solution Approach 1:
The patent modifies the physical and chemical parameters of donepezil delivery by incorporating it into PLGA/PLA polymer matrices with specific molecular weights and ratios, changing the release kinetics from high burst effect to controlled sustained release, thereby improving therapeutic index
Solution Approach 2:
The patent creates a localized controlled release environment at the injection site where donepezil is released gradually from the polymer matrix, providing consistent local drug concentration that improves therapeutic efficacy while reducing systemic adverse reactions
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 composition provides a controlled release of donepezil with a reduced burst effect, improved therapeutic index, and lower incidence of adverse reactions, offering a more effective treatment for the mentioned diseases.
Implementation Method 1
a bioerodible and biodegradable release retardant polymer that includes polylactic-co-glycolic acid) (PLGA), polylactide (PLA), or a combination thereof
Implementation Method 2
a biocompatible solvent that includes N-methyl pyrrolidone
Data Source
AI summary
A liquid injectable composition comprising:(a) a bioerodible and biodegradable, release retardant polymer comprising polylactic-ccs-glycolic acid) (PLEA), polylactide (PLA), or combination thereof;(b) a biocompatible solvent selected from dimethylsulfoxide, 2-pyrrolidone, N,N-dimethyl acetamide, dimethylformamide, glycofurol, glycerol formal, propylene glycol, benzyl benzoate, N-methyl-2-pyrrolidone, benzyl alcohol, or combination thereof; and(c) donepezil, in the free base or pharmaceutically acceptable salts thereof.