Stability and Aerosol Performance of an excipient-free dry powder of Tigecycline for local delivery in lung infections

Varsha Nair¹, Hugh D.C Smyth¹

¹The University of Texas at Austin, 2409 University Avenue, Austin, 78705, USA

Summary

Tigecycline (TIG) is a broad-spectrum antibiotic that is susceptible against a wide variety of bacteria. It is currently marketed as Tygacil®, an intravenous injection. However, TIG undergoes rapid degradation upon exposure to an aqueous environment and must be only reconstituted at the time of administration. Through this study, a dry micronization process, air jet milling, was utilized to reduce the TIG powders into a respirable particle size range. Neat micronized TIG was found to have enhanced aerosolization efficiency as well as stability as a dry powder for inhalation. The micronized powders were compared to the non-micronized or unmilled powder to detect any degradation that may occur due to processing. The excipient free formulation also enables high dose delivery while maintaining a lower powder payload for the patients. Further, to ensure efficient delivery and storage of TIG, it was subjected to storage stability studies as per ICH guidelines. TIG powders remained stable upon storage at high temperatures and relative humidity for 6 months. Micronized TIG powders also had little to no propensity to absorb moisture thereby facilitating the storage stability of the powders further. Additionally, the micronized powders also maintained their aerosolization efficiency with no difference between Day 0 and the 6-month time point at 25°C/60% RH and a slight difference at  40°C/75% RH. Thus, an excipient free, inhalable, high dose dry powder of TIG exhibiting promising storage stability was developed.

Key Message

Degradation prone, unstable antibiotic TIG was successfully developed as an excipient free dry powder formulation that showed stability and lack of water absorption for 6 months upon storage at intermediate and accelerated conditions.