Apomorphine Buccal Composition for Rapid Absorption
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Solution Overview
Problem
Current apomorphine formulations for treating Parkinson's disease and male erectile dysfunction face challenges such as rapid metabolism, nasal irritation, and delayed absorption, limiting their efficacy and convenience, especially for rapid 'on-off' fluctuations in Parkinson's disease.
Innovation Solution
A composition of apomorphine in a non-aqueous solution or suspension, preferably with a propellant like HFA134a, which is degassed to prevent oxidation, and has a pH optimized for buccal or sublingual administration, ensuring rapid absorption and stability, eliminating the need for acidic environments and complex delivery systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If apomorphine is administered orally, then the drug can be given conveniently, but rapid first-pass metabolism occurs and very little unmetabolized drug reaches circulation
Solution Approach 1:
The patent extracts apomorphine from the gastrointestinal tract absorption pathway by using buccal or sublingual administration. The drug is placed in the cheek pouch or under the tongue where it absorbs directly into the bloodstream through the mucous membrane, bypassing the liver's first-pass metabolism that would otherwise destroy most of the orally administered drug.
Solution Approach 2:
The patent introduces a propellant-based non-aqueous solution as an intermediary vehicle to deliver apomorphine to the buccal or sublingual mucosa. This propellant formulation enables the drug to be held in the cheek pouch or under the tongue long enough for complete absorption, serving as a mediator between oral administration and systemic delivery.
2Speed
If apomorphine is administered subcutaneously, then rapid onset of action occurs within 5 to 15 minutes, but the necessity for injection reduces ease of administration
Solution Approach 1:
The patent replaces the mechanical injection system with a non-invasive buccal or sublingual administration system. The propellant-based formulation allows the drug to be delivered through the mucous membrane without needles or syringes, substituting a mechanical injection process with a simpler topical application process that achieves comparable rapid absorption.
3Ease of operation
If apomorphine is formulated in aqueous solution, then the drug can be administered easily, but oxidation occurs rapidly requiring acidic environments and complex delivery systems
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using a non-aqueous propellant-based solution instead of an aqueous solution. This parameter change eliminates the need for acidic environments and complex delivery systems, as the propellant medium prevents oxidation while allowing easy buccal or sublingual administration.
Solution Approach 2:
The patent creates an inert environment by using a propellant-based non-aqueous solution that excludes oxygen and water from contact with apomorphine. This inert atmosphere prevents oxidation of the drug during storage and administration, eliminating the need for acidic stabilizers or complex protective delivery systems.
4Speed
If intranasal apomorphine is administered, then the drug can be delivered rapidly, but transient nasal blockage and burning sensation occur
Solution Approach 1:
The patent extracts the drug delivery site from the nasal cavity to the buccal or sublingual mucosa. By placing apomorphine in the cheek pouch or under the tongue using the propellant formulation, the patent avoids the harmful nasal irritation effects while maintaining rapid absorption through the richly vascularized mucous membrane.
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 formulation provides rapid and stable absorption of apomorphine, reducing the risk of oxidation and improving the speed and efficacy of treatment for Parkinson's disease and male erectile dysfunction, while minimizing side effects and enhancing convenience through optimized pH and solvent choice.
Implementation Method 1
A composition of apomorphine in a non-aqueous solution or suspension, preferably with a propellant like HFA134a, which is degassed to prevent oxidation
Implementation Method 2
which is degassed to prevent oxidation
Implementation Method 3
ensuring rapid absorption and stability, eliminating the need for acidic environments
Data Source
AI summary
Compositions and devices comprising apomorphine or pharmaceutically acceptable salts are described. The compositions may comprise a solution of apomorphine, or a pharmaceutically acceptable salt thereof, and a propellant. The solution may be a non-aqueous solution or an aqueous solution comprising degassed water. Devices may be configured to deliver compositions in form of particles or droplets having a mass median aerodynamic diameter (MMAD) or volume median diameter (VMD) greater than 10 pm; and/or a fine particle fraction (FRF) less than 30%.