Preparation and evaluation of tilmicosin microspheres and lung-targeting studies in rabbits

Area of Science:

• Veterinary Pharmacology
• Drug Delivery Systems
• Macrolide Antibiotics

Background:

• Tilmicosin (TMS) is a crucial macrolide antibiotic for treating veterinary pulmonary infections.
• Conventional TMS administration faces challenges due to frequent dosing requirements and a short elimination half-life.
• There is a need for improved TMS formulations to enhance therapeutic efficacy and patient compliance.

Purpose of the Study:

• To develop and characterize tilmicosin-gelatine microspheres (TMS-GMS) as a sustained-release formulation.
• To evaluate the in vitro and in vivo pharmacokinetic properties of TMS-GMS in rabbits.
• To assess the lung-targeting potential and prolonged elimination half-life of the novel TMS-GMS formulation.

Main Methods:

• Tilmicosin-gelatine microspheres (TMS-GMS) were prepared using an emulsion-chemical cross-linking technique.
• Characterization included particle size analysis, in vitro drug release studies, and stability testing (light and thermal).
• Pharmacokinetic (PK) studies were conducted in rabbits following intramuscular injection of TMS-GMS and conventional TMS.

Main Results:

• TMS-GMS exhibited spherical morphology with a mean diameter of 11.34±1.20μm, suitable for sustained release.
• In vitro studies showed a slower release of TMS from TMS-GMS compared to crude TMS.
• In vivo PK analysis in rabbits revealed a significantly prolonged elimination half-life (59.21h vs. 38.56h in lung) and enhanced lung targeting (C_e ratio of 2.19) for TMS-GMS.

Conclusions:

• Tilmicosin-gelatine microspheres (TMS-GMS) represent a promising sustained-release formulation for tilmicosin.
• The TMS-GMS formulation offers the advantages of a prolonged elimination half-life and improved lung-targeting capabilities.
• These characteristics suggest potential for enhanced therapeutic outcomes in veterinary clinical applications for pulmonary infections.