The optimization of an intravaginal ring releasing progesterone using a mathematical model

Area of Science:

• Reproductive Medicine
• Materials Science
• Drug Delivery Systems

Background:

• Progering® is the sole intravaginal ring for contraception during lactation, utilizing silicone to release progesterone.
• Concerns regarding silicone's properties necessitate exploring alternative materials for improved contraceptive devices.

Purpose of the Study:

• To evaluate ethylene vinyl acetate copolymer (EVA) as a substitute material for silicone in intravaginal progesterone-releasing contraceptive rings.
• To design and characterize EVA rings for controlled progesterone release during lactation.

Main Methods:

• EVA rings were fabricated using hot-melt extrusion.
• In vitro assays assessed swelling, degradation, and progesterone release kinetics in ethanol/water mixtures.
• Solubility, partition coefficient, initial hormone load, and ring dimensions were analyzed.
• A mathematical model guided the design for a specific hormone release rate.

Main Results:

• Successfully designed EVA rings achieved an in vitro progesterone release rate of approximately 12.05 ± 8.91 mg/day, comparable to Progering®.
• Increased initial hormone load and ring dimensions correlated with higher progesterone release rates.
• Extended device lifespan was observed with higher initial hormone loads.

Conclusions:

• EVA rings demonstrate potential for progesterone delivery in contraception during lactation, achieving a target release rate of 12.05 ± 8.91 mg/day.
• EVA offers potential advantages including reduced hormone content, simplified manufacturing (no curing/crosslinking), lower costs, and recyclability.
• EVA represents a promising alternative material for developing next-generation contraceptive vaginal rings.