Apomorphine Composition Stabilization Without Antioxidants
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Solution Overview
Problem
Apomorphine hydrochloride aqueous solutions are unstable due to oxidation susceptibility, leading to injection site reactions and difficulties in administration for Parkinson's disease patients, particularly with complex device handling requirements.
Innovation Solution
A stable pharmaceutical composition of apomorphine with pharmaceutically acceptable carriers, stabilizers, isotonicity agents, and buffering agents, formulated to maintain a pH between 3 and 4, packaged in a unit dose device like an autoinjector or prefilled syringe, and protected from oxidation using inert gases, minimizing adverse reactions and simplifying administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If antioxidants such as sodium metabisulfite are used to improve stability of apomorphine hydrochloride in aqueous solution, then oxidation resistance is improved, but injection site reactions and hypersensitivity occur
Solution Approach 1:
The invention removes harmful antioxidants (sodium metabisulfite, benzyl alcohol) from the formulation while maintaining stability through alternative means - specifically by controlling pH (3.0-4.0) and using oxygen-impermeable packaging, thereby eliminating injection site reactions while preserving drug stability
Solution Approach 2:
The invention uses oxygen-impermeable packaging materials and maintains an oxygen-excluded environment during storage and administration to prevent oxidation of apomorphine hydrochloride without requiring chemical antioxidants, thus avoiding hypersensitivity reactions
2Stability of the object's composition
If benzyl alcohol is used as a preservative to maintain stability, then microbial contamination is prevented, but skin necrosis and local site irritation occur
Solution Approach 1:
The invention eliminates benzyl alcohol and other harmful preservatives from the formulation, relying instead on pH control (3.0-4.0) and oxygen-impermeable packaging to maintain stability without causing skin necrosis or local irritation
Solution Approach 2:
The invention employs single-use pre-filled syringes that are discarded after one administration, eliminating the need for preservatives entirely since the product is not stored after opening, thus avoiding preservative-related adverse events
3Measurement precision
If a multistep device is used for administration of apomorphine, then precise dosing control is achieved, but device complexity and difficulty of operation increase
Solution Approach 1:
The invention integrates the dosing mechanism, delivery system, and safety features into a single simplified pre-filled syringe design that requires minimal steps for administration, combining multiple functions into one unified device that is easy for patients to operate
Solution Approach 2:
The invention prepares the device in advance with pre-filled, pre-primed syringes that require no assembly or complex preparation steps by the patient, with dose markings pre-indicated on the plunger for straightforward administration
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 provides enhanced stability and patient compliance by reducing pain associated with subcutaneous administration and eliminating complex device handling steps, while maintaining apomorphine potency and minimizing impurities and oxidation risks.
Implementation Method 1
A well-known problem of aqueous solutions of apomorphine hydrochloride is stability, since the compound is highly susceptible to oxidation
Data Source
AI summary
The present invention provides a stable pharmaceutical composition comprising apomorphine and one or more pharmaceutically acceptable carriers in an injectable device. The present invention also provides a process for preparing the stable pharmaceutical composition.