Donepezil Memantine Composition Controlled Release
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Solution Overview
Problem
Current therapeutic methods for Alzheimer-type dementia using donepezil and memantine face challenges in compliance due to frequent administration, differing solubilities, and lack of controlled release methods, leading to difficulties in managing the blood concentration profiles and gastric emptying time effects.
Innovation Solution
A composition comprising donepezil and memantine with a sustained-release portion using non-pH-dependent and pH-dependent polymeric substances like ethylcellulose and methacrylic acid-ethyl acrylate copolymer, allowing for controlled release profiles that can be adjusted for acidic and neutral solutions, enabling once-daily administration and improved compliance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If commercially available donepezil and memantine products are used together, then the therapeutic effect on dementia is achieved, but the frequency of administration and amount taken are high, leading to poor compliance
Solution Approach 1:
The patent combines two separate anti-dementia medications (donepezil hydrochloride and memantine hydrochloride) into a single fixed-dose combination tablet. This merging allows patients to take both drugs simultaneously in one administration, reducing the total number of tablets from three (one donepezil + two memantine) to one, thereby improving compliance while maintaining the required therapeutic doses of both medications.
Solution Approach 2:
The patent performs preliminary formulation work to create a stable fixed-dose combination product that accounts for the different solubilities and release characteristics of donepezil and memantine. By pre-engineering the tablet with appropriate excipients and release mechanisms, the product ensures consistent blood concentration profiles and eliminates the need for patients to manage multiple separate medications, thus improving ease of administration before the patient even takes the medication.
2Ease of operation
If donepezil and memantine are combined in a single dosage form, then compliance is improved, but the drugs have different solubilities and pKa values making it difficult to simultaneously control the release of both drugs
Solution Approach 1:
The patent applies local quality by using different excipient compositions and coating strategies for different portions of the tablet formulation. Specifically, it employs enteric-coated memantine granules that resist dissolution in acidic stomach environment but release in the more neutral intestinal environment, while donepezil is formulated to release more quickly. This localized differentiation of release properties within the single tablet enables simultaneous control of both drugs despite their different solubility characteristics.
Solution Approach 2:
The patent uses composite materials in the tablet formulation, combining donepezil hydrochloride with memantine hydrochloride in a single matrix along with multiple excipients including binders, disintegrants, and coating materials. The enteric coating layer acts as a composite barrier that selectively controls drug release based on pH conditions, enabling precise control of both medications' release profiles within one dosage form despite their different pKa values and solubilities.
3Ease of manufacture
If the release of anti-dementia drugs is not controlled, then manufacturing is simpler, but the blood concentration profiles are affected by gastric emptying time and solubility differences
Solution Approach 1:
The patent applies parameter changes by modifying the physical and chemical parameters of the drug formulation, specifically by using enteric-coated granules that change their dissolution behavior based on pH parameters. The coating material is designed to remain intact at gastric pH levels but dissolve at intestinal pH levels, thereby changing the release parameter from immediate to delayed. This parameter modification stabilizes the blood concentration profile by ensuring both drugs are released in the intestine rather than being subject to variable gastric emptying rates.
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 achieves a synergistic effect between donepezil and memantine, providing a stable and effective therapeutic method with improved patient compliance, reduced burden on caregivers, and simplified manufacturing, while maintaining consistent blood concentration profiles regardless of gastric emptying time.
Implementation Method 1
a pH-dependent polymeric substance which comprises at least one selected from a methacrylic acid-ethyl acrylate copolymer, a methacrylic acid-methyl methacrylate copolymer, hydroxypropyl methylcellulose phthalate, and hydroxypropyl methylcellulose acetate succinate
Data Source
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AI summary
An object of the present invention is to provide, for the case of implementing a therapeutic method in which at least two kinds of anti-dementia drugs are used together, a composition that has a good therapeutic effect on dementia, and also gives excellent compliance. Another object of the present invention is to provide a composition containing at least two kinds of anti-dementia drugs, in which release of the anti-dementia drugs from the composition is controlled, whereby a combined effect of the anti-dementia drugs can be achieved well. Still another object of the present invention is to provide a composition for which the frequency of administration and the amount taken are reduced and hence compliance can be improved, and a method of manufacturing such a composition. According to the present invention, there is provided a composition containing at least two kinds of anti-dementia drugs; such a composition containing at least one sustained-release portion containing an anti-dementia drug; and such a composition containing at least one cholinesterase inhibitor, and at least one N-methyl-D-aspartate receptor antagonist.