Permethylated Cyclodextrin Complex for Drug Delivery
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Solution Overview
Problem
Current pharmaceutical preparations face challenges in achieving predictable and reliable delivery of active substances to the intended site of action due to issues with solubility and bioavailability, particularly in oral administration, where benzodiazepines like midazolam have variable bioavailability and delayed onset, and transmucosal applications where penetration through mucosa is slow, leading to inadequate anxiolysis in preoperative settings.
Innovation Solution
A pharmaceutical preparation using a permethylated cyclodextrin with a degree of substitution of 3 methyl groups per glucopyranose unit forms a complex with a pharmaceutical active substance having an aromatic group, enhancing solubility and membrane penetration, allowing for rapid and reliable delivery of the active substance through the formation of a stable, non-aggregated complex with improved lipophilicity and water solubility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral administration of benzodiazepines is used for anxiolysis, then the active substance can be delivered to the systemic circulation, but the bioavailability is variable and the accumulation time is too long (45-60 min) for modern surgical scheduling requirements
Solution Approach 1:
The patent uses cyclodextrin complexes as intermediary carriers to transport the benzodiazepine active substance across the mucosal barrier. The cyclodextrin forms inclusion complexes with the drug, facilitating rapid trans-mucosal absorption and reducing accumulation time from 45-60 minutes to approximately 15 minutes, while maintaining reliable and predictable bioavailability.
2Quantity of substance
If water-soluble active substances are used for intravenous administration, then high systemic concentration can be attained, but insufficient lipophilicity results in low bioavailability due to poor penetration through cell membranes at the intended site of action
Solution Approach 1:
The cyclodextrin complex acts as an intermediary that bridges the contradiction between water solubility and membrane penetration. The complex itself is water-soluble, enabling high systemic concentration delivery, while the lipophilic active substance within the complex can effectively penetrate cell membranes at the site of action, ensuring reliable bioavailability.
3Speed
If transmucosal application is used to improve absorption speed, then the active substance can reach systemic circulation faster, but penetration through the mucosa remains slow and bioavailability is insufficient for adequate anxiolysis
Solution Approach 1:
The cyclodextrin complex serves as an intermediary that enhances both the speed and reliability of trans-mucosal absorption. The complex facilitates rapid penetration through the mucosal barrier while maintaining sufficient bioavailability for adequate anxiolytic effect, resolving the contradiction between fast absorption and reliable drug delivery.
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 permethylated cyclodextrin complex enables rapid and predictable systemic concentration of the active substance, improving bioavailability and anxiolytic effects, as demonstrated by faster serum level attainment and longer action duration in transmucosal applications, and facilitating intravenous administration of insoluble substances like propofol with reduced equipotent doses and minimized side effects.
Implementation Method 1
permethylated cyclodextrin and pharmaceutical active substance form a complex
Implementation Method 2
The complete absence of OH groups, which results from permethylation, promotes the entry of hydrophobic pharmaceutical active substances (aromatic group or aromatic moiety) into the cavity for the purpose of complexing
Data Source
AI summary
The invention relates to a pharmaceutical preparation for applying a pharmaceutical agent. According to the invention, the preparation contains: a) a pharmaceutical agent which has an aromatic group or an aromatic part and the molecule of which has a maximum diameter of ≦2 nm; b) a permethylated cyclodextrin having a degree of substitution of 3 methyl groups per glucopyranose unit. The permethylated cyclodextrin and the pharmaceutical agent form a complex.