Impact of Mixing Approach and Bubble Formation on In Situ Forming Implant Properties

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• In situ forming implants (ISFIs) are advanced drug delivery systems.
• Commercial ISFIs utilize either dual-syringe mixing or pre-mixed formulations.
• The method of mixing can influence the final properties and performance of ISFIs.

Purpose of the Study:

• To compare the effects of pre-injection syringe mixing versus ready-to-inject formulations on ISFIs.
• To evaluate how different mixing approaches impact ISFI properties and in vitro performance.
• To provide a reference for developing future ISFI products.

Main Methods:

• Computed tomography (CT) and scanning electron microscopy (SEM) for structural and morphological analysis.
• High-performance liquid chromatography (HPLC) for drug release studies.
• Gel permeation chromatography (GPC) for polymer degradation assessment.

Main Results:

• Ready-to-inject ISFIs showed a uniform polymer matrix without air bubbles, unlike syringe-mixed ISFIs.
• Air bubbles in syringe-mixed ISFIs led to slower solvent release, altered drug deposition, increased volume expansion, and faster initial degradation.
• CT imaging indicated more uniform structures in ready-to-inject implants compared to heterogeneous cavities in syringe-mixed implants.

Conclusions:

• Pre-injection mixing, leading to air bubbles, can negatively affect ISFI drug release and performance.
• The choice of mixing technique is critical for controlling ISFI characteristics.
• This comparative study offers valuable insights for ISFI product development.