Δ9-THC Prodrug Compositions for Transdermal Systemic Delivery
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Solution Overview
Problem
Δ9-tetrahydrocannabinol (Δ9-THC) undergoes substantial first-pass metabolism when absorbed from the human gut after oral administration, leading to diminished oral bioavailability, and is poorly absorbed through mammalian skin due to its hydrophobic nature, limiting successful transdermal administration of therapeutically effective quantities.
Innovation Solution
Development of Δ9-THC prodrugs that are metabolized in the skin to produce systemically available Δ9-THC, suitable for transdermal and other routes of administration, including oral, buccal, sublingual, injectable, topical, follicular, nasal, ocular, and vaginal delivery, to treat medical conditions such as pain, nausea, and appetite stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Δ9-THC is administered orally, then it can be delivered to the systemic circulation, but it undergoes substantial first-pass metabolism leading to diminished oral bioavailability
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of Δ9-THC to create prodrugs with altered physicochemical properties. Specifically, the prodrugs are designed to have improved water solubility and reduced affinity for metabolic enzymes, thereby changing the metabolic parameters and achieving systemic availability without substantial first-pass metabolism
Solution Approach 2:
The patent uses an intermediary approach by introducing prodrug moieties that serve as mediators between the administered compound and the target cannabinoid receptors. These prodrugs are metabolized in the body to release the active Δ9-THC, thereby mediating the delivery process and avoiding direct first-pass metabolism of the active compound
2Quantity of substance
If Δ9-THC is applied topically for transdermal delivery, then it can be delivered directly to the skin and deeper tissues, but its hydrophobic nature causes poor absorption through mammalian skin
Solution Approach 1:
The patent applies parameter changes by modifying the lipophilicity parameter of Δ9-THC through prodrug design. The prodrugs are engineered to have optimized log P values that balance skin penetration capability with systemic absorption, thereby overcoming the hydrophobicity barrier while maintaining therapeutic efficacy
Solution Approach 2:
The patent uses penetration enhancers and formulation excipients as intermediaries to facilitate transdermal delivery. These intermediaries temporarily interact with the prodrug molecules and the skin barrier, mediating the transport process and enabling effective delivery without requiring the active compound itself to be highly lipophilic
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 Δ9-THC prodrugs enable systemic delivery of therapeutically effective amounts of Δ9-THC, overcoming first-pass metabolism and skin absorption limitations, while also allowing localized topical administration to alleviate skin and deeper tissue conditions.
Implementation Method 1
Δ9-THC prodrugs that are metabolized in the skin to produce systemically available Δ9-THC
Data Source
AI summary
Described herein are Δ9-THC prodrugs, methods of making Δ9-THC prodrugs, formulations comprising Δ9-THC prodrugs and methods of using Δ9-THC. One embodiment described herein relates to the transdermal administration of a Δ9-THC prodrug for treating and preventing diseases and/or disorders.