Donepezil Topical Formulation for Higher Intradermal Retention
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Solution Overview
Problem
Existing formulations fail to effectively deliver donepezil intradermally due to the skin's barrier properties, leading to low permeation and retention, and there is a need for a formulation that enhances skin penetration and maintains therapeutic dermal concentration.
Innovation Solution
Compositions comprising donepezil, 2-(2ethoxyethoxy) ethan-1-ol, a fatty acid ester, and a monohydric alcohol, optionally with low molecular weight polyethylene glycol, are formulated for intradermal delivery, achieving at least twice the dermal concentration compared to transdermal delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If transdermal formulation is used to deliver donepezil, then systemic delivery is achieved, but intradermal concentration is insufficient
Solution Approach 1:
The formulation changes the chemical parameters by incorporating penetration enhancers (2-(2ethoxyethoxy) ethan-1-ol, fatty acid esters, and monohydric alcohols) that modify the stratum corneum's permeability properties, enabling higher intradermal concentrations of donepezil to be achieved topically
Solution Approach 2:
Penetration enhancers act as intermediary substances that facilitate the transfer of donepezil through the stratum corneum barrier, with 2-(2ethoxyethoxy) ethan-1-ol and fatty acid esters serving as mediators that increase drug flux and intradermal retention
2Quantity of substance
If topical formulation is applied to overcome skin barrier, then skin penetration is enhanced, but adverse effects like eczema and pruritis occur
Solution Approach 1:
The formulation optimizes the concentration parameters of penetration enhancers to achieve effective skin penetration while maintaining safety, using specific ratios of 2-(2ethoxyethoxy) ethan-1-ol, fatty acid esters, and monohydric alcohols that enhance permeation without causing irritation
Solution Approach 2:
The formulation uses a composite approach by combining multiple penetration enhancers (2-(2ethoxyethoxy) ethan-1-ol, fatty acid esters, and monohydric alcohols) with donepezil, where the synergistic interaction of these components achieves effective delivery while reducing individual component toxicity
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 compositions enhance intradermal delivery of donepezil, providing therapeutic benefits for conditions like psoriasis, atopic dermatitis, and acne by maintaining higher dermal concentrations and improving treatment efficacy.
Implementation Method 1
passive methods employ chemical or molecular means to enhance stratum corneum permeability. The most appealing passive methods entail use of molecular penetration enhancers, or MPEs, molecules which interact with the structure of the stratum corneum at the molecular level to facilitate molecule ingress by one or more of several mechanisms, for example, by disrupting the lipid bilayers of the stratum corneum
Implementation Method 2
The challenge of delivering a drug molecule through the main barrier to ingress, the outermost layer of the epidermis called the stratum corneum, and maintaining an intradermal concentration of the drug
Data Source
AI summary
The invention provides compositions comprising a topical formulation of donepezil and methods of use thereof for intradermal applications.