Subcutaneous MPA Suspension Composition for Heat-Stable Shelf Life
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Solution Overview
Problem
Existing medroxyprogesterone acetate (MPA) compositions face challenges in maintaining extended shelf life and duration of action under extreme conditions of high heat, high humidity, and unreliable electricity and refrigeration, which are prevalent in underdeveloped regions, leading to poor patient compliance due to frequent medical visits.
Innovation Solution
Aqueous compositions containing MPA at 260-350 mg/ml, docusate sodium at 0.6-1.3 mg/ml, and polyethylene glycol at 10-40 mg/ml, optimized for subcutaneous injection, providing enhanced stability, extended shelf life, and improved syringeability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If MPA composition is stored under extreme conditions (high heat, high humidity), then shelf life is reduced and stability deteriorates, but refrigeration infrastructure is unreliable or unavailable in underdeveloped regions
Solution Approach 1:
The patent modifies the physical and chemical parameters of the MPA composition, specifically adjusting the particle size distribution (d(90) of 9-30 μm), concentration (400 mg/ml), and formulation components (docusate sodium, polyethylene glycol) to achieve enhanced thermal stability and extended shelf life under extreme temperature conditions up to 50°C
Solution Approach 2:
The invention creates a composite formulation combining MPA with specific excipients including docusate sodium and polyethylene glycol in optimized ratios, forming a stable suspension system that maintains potency and physical integrity under varying temperature and humidity conditions without requiring refrigeration
2Duration of action of moving object
If MPA concentration is increased to extend duration of action, then injection viscosity increases and syringeability deteriorates, but long-acting formulation is needed to reduce medical visits
Solution Approach 1:
The patent optimizes the particle size distribution parameter (d(90) of 9-30 μm) and concentration (400 mg/ml) to achieve a balance between extended duration of action and maintainable syringeability, allowing high-dose long-acting formulation to be easily administered via subcutaneous injection
Solution Approach 2:
The formulation incorporates docusate sodium and polyethylene glycol as intermediary substances that act as surfactants and viscosity modifiers, reducing injection resistance and improving syringeability of the high-concentration MPA suspension without compromising the extended duration of action
Data Source
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AI summary
The disclosure is directed to medroxyprogesterone compositions suitable for subcutaneous injection comprising about 260 mg/ml to 440 mg/ml medroxyprogesterone acetate, about 0.6 mg/ml to 1.5 mg/ml docusate sodium and, polyethylene glycol. Methods of using these compositions are also described.