Mitomycin-C Syringe Kit pH Stability and Compounding
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Solution Overview
Problem
Current methods fail to provide stable and compliant pre-filled syringe kits for Mitomycin-C, particularly for intravesical bladder instillation, due to challenges in maintaining drug stability and compliance with hazardous compounding regulations, especially in smaller healthcare facilities.
Innovation Solution
A formulation of Mitomycin-C with 0.9 mg/mL to 1.2 mg/mL concentration, 300 mg/mL to 550 mg/mL propylene glycol, and 0.1 mg/mL to 10 mg/mL sodium phosphate buffer, combined with a closed system transfer device, is developed to create a stable and ready-to-administer syringe kit, suitable for production in a 503B Outsourcing facility, maintaining pH stability between 7.0 and 8.0 even in acidic environments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Mitomycin-C is compounded in traditional settings, then flexibility and accessibility are improved, but drug stability and compliance with hazardous compounding regulations deteriorate
Solution Approach 1:
The patent applies preliminary action by pre-compounding Mitomycin-C in FDA-approved hazardous drug facilities with proper USP-level preparations and handling facilities before distribution to clinics. This allows small clinics without hazardous drug compounding capabilities to access stable, compliant Mitomycin-C formulations, resolving the contradiction between accessibility and regulatory compliance.
2Ease of operation
If Mitomycin-C is stored in aqueous solutions, then ease of administration is improved, but drug stability deteriorates due to degradation in acidic and alkaline environments
Solution Approach 1:
The patent applies parameter changes by formulating Mitomycin-C in a non-aqueous vehicle (such as propylene glycol or other approved vehicles) rather than traditional aqueous solutions. This fundamental change in the solvent parameter prevents drug degradation in acidic and alkaline environments while maintaining ease of administration through intravesical instillation.
Solution Approach 2:
The patent applies composite materials by creating a formulation that combines Mitomycin-C with specific vehicles and stabilizers (such as propylene glycol, and in some embodiments, antioxidants or chelating agents) to achieve both stability and ease of administration. This composite formulation resolves the contradiction between drug stability and ease of use.
3Reliability
If outsourcing compounding to 503B facilities is done, then compliance with hazardous drug regulations is improved, but availability of suitable closed system transfer devices and stable formulations deteriorates
Solution Approach 1:
The patent applies segmentation by dividing the compounding process into two distinct segments: (1) manufacturing in FDA-approved 503B outsourcing facilities with proper hazardous drug handling capabilities, and (2) administration at local clinics using pre-filled syringes. This segmentation allows compliance to be achieved at the manufacturing level while simplifying the administration process at the clinic level.
Solution Approach 2:
The patent applies the principle of disposable objects by providing pre-filled single-use syringes that are disposed of after a single administration. This eliminates the need for clinics to invest in expensive closed system transfer devices while maintaining compliance with hazardous drug handling requirements through proper disposal protocols.
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 maintains stability and efficacy of Mitomycin-C for over 134 days, preventing degradation and precipitation, and the kit ensures compliance with USP hazardous compounding regulations, providing a safe and effective solution for bladder cancer treatment.
Implementation Method 1
0.1 mg/mL to 10 mg/mL (0.01% and 1.0% weight/volume) sodium phosphate buffer
Implementation Method 2
300 mg/mL to 550 mg/mL (30% to 55% weight/volume) propylene glycol
Data Source
AI summary
The disclosure provides compositions, methods, and devices for use in delivering Mitomycin-C(MMC), an antineoplastic chemotherapy drug often used for bladder instillations to treat bladder cancer, which degrades in both acidic and alkaline environments. The disclosure provides a solution of buffered MMC (or a different drug) in 50% propylene glycol that maintains a pH from 7.0 to 8.0 when introduced into acidic solutions (pH of 5.0) and is stable when stored at 2-8° C. for greater than 134 days. This formulation can be produced in an FDA registered 503B Outsourcing facility in a pre-filled, ready-to-administer syringe kit with pre-attached closed system transfer device and accessories required for bladder instillation.