Preparation and evaluation of Tilmicosin (cas 108050-54-0) microspheres and lung-targeting studies in rabbits
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Add time:08/22/2019 Source:sciencedirect.com
Tilmicosin (cas 108050-54-0) (TMS) is a macrolide used extensively for pulmonary infections in clinical veterinary medicine. However, TMS has frequent administration and short elimination half-life. Therefore, tilmicosin–gelatine microspheres (TMS–GMS) were prepared by an emulsion-chemical cross-linking technique as a sustained-release formulation to extend drug half-life. The particle size distribution, in-vitro sustained-release properties, stability, and physical characteristics, as well as pharmacokinetic (PK) characteristics, were evaluated in rabbits.TMS–GMS were spherical in shape and had a mean diameter of 11.34 ± 1.20 μm; 95.65% of the microspheres varied in size from 5.0 to 25.0 μm. Light and thermal stability tests indicated no significant changes in all observed indices. Importantly, compared to crude TMS, slower release of TMS from TMS–GMS was noted in drug release studies (in vitro). Pharmacokinetic (PK) characteristics were examined in the lung, liver, heart, kidney and muscle tissue of rabbits following IM injection of TMS–GMS or TMS-injection at a dose of 10 mg/kg. The elimination half-life of TMS–GMS (59.21 ± 0.21 h) was longer than that of TMS-injection (38.56 ± 0.13 h) in the lung. The ratio of peak concentration (Ce) of TMS–GMS to TMS-injection was 2.19 (>1) in the lung, demonstrating the selectivity of TMS–GMS to target the lung compared to that of other tissues (Ce < 1). Interestingly, the uptake value of TMS from TMS–GMS was 8.48 times higher in the lung than that for the TMS-injection, and was slightly higher than in the liver (1.85), heart (1.72), kidney (2.44) and muscle (2.79) tissues. TMS–GMS is a sustained-release formulation of TMS with potential to be used in veterinary clinical applications; possible benefits include lung-targeting and prolonged elimination half-life.
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