The Relationship Between Structures and In Vitro Properties of a Polyanhydride Implant Containing Gentamicin Sulfate

Abstract

Laboratory scale injection-molding equipment was utilized to fabricate an implant consisting of poly(FAD:SA 1:1) and 20% (w/w) gentamicin sulfate. Characterizations were performed to determine the molecular weight and glass transition temperature of poly(FAD:SA 1:1). A study was carried out to investigate the relationships between the in vitro performance, morphology, and micro-structures of the molded implants. It was found that implants produced with different structures exhibited different physical integrities in water, i.e., cracking or non-cracking. For the non-cracking implants, a skin–core structure formed by an oriented skin layer was observed under a polarized light microscope. The same morphology was not seen in the cracking implants. The crystal orientation in the skin layer of the non-cracking implants was further identified using a wide-angle x-ray diffraction method (WAXD). No crystal orientation could be found in the cracking implants by WAXD. Furthermore, studies were carried out to evaluate the in vitro drug release for implants showing different degrees of integrity in water. The in vitro drug release of the cracking implants was markedly faster than that of the non-cracking implants due to the pronounced initial drug-burst effect as a result of crack formation in the implants.

Keywords:

• Cracking
• Crystal orientation
• Drug-burst effect
• Gentamicin sulfate
• Implant
• In vitro drug release
• In vitro performance
• Injection-molding
• Micro-structures
• Morphology
• Non-cracking
• Physical integrities
• Poly(FAD:SA 1:1)
• Skin–core structure