Inhalable Excipient-Free Dry Powder of Tigecycline for the Treatment of Pulmonary Infections.

Tigecycline (TIG) is a broad-spectrum antibiotic that has been approved for the treatment of a number of complicated infections, including community-acquired bacterial pneumonia. Currently it is available only as an intravenous injection that undergoes rapid chemical degradation and limits the use to in-patient scenarios. The use of TIG as an inhaled dry powder inhaler may offer a promising treatment option for patients with multidrug-resistant respiratory tract infections, such as Stenotrophomonas maltophilia (S. maltophilia). This study explores the feasibility of engineering an inhaled powder formulation of TIG that could administer relevant doses at a wide range of inhalation flow rates while maintaining stability of this labile drug. Using air-jet milling, micronized TIG had excellent aerosolization efficiency, with over 80% of the device emitted dose being within the respirable range. TIG was also readily dispersed using different inhaler devices even when tested at different pressure drops and flow rates. Additionally, micronized TIG was stable for 6 months at 25 °C/60% RH and 40 °C/75% RH. Micronized TIG maintained a low minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of 0.8 µM and >0.5 µM, respectively in S. maltophilia cultures in vitro. These results strongly suggest that the micronization of TIG results in a stable and respirable formulation that can be delivered via the pulmonary route for the treatment of lung infections.

Buccal delivery of small molecules and biologics: Of mucoadhesive polymers, films, and nanoparticles - An update.

Buccal delivery of small and large molecules is an attractive route of administration that has been studied extensively over the past few decades. This route bypasses first-pass metabolism and can be used to deliver therapeutics directly to systemic circulation. Moreover, buccal films are efficient dosage forms for drug delivery due to their simplicity, portability, and patient comfort. Films have traditionally been formulated using conventional techniques, including hot-melt extrusion and solvent casting. However, newer methods are now being exploited to improve the delivery of small molecules and biologics. This review discusses recent advances in buccal film manufacturing, using the latest technologies, such as 2D and 3D printing, electrospraying, and electrospinning. This review also focuses on the excipients used in the preparation of these films, with emphasis on mucoadhesive polymers and plasticizers. Along with advances in manufacturing technology, newer analytical tools have also been used for the assessment of permeation of the active agents across the buccal mucosa, the most critical biological barrier and limiting factor of this route. Additionally, preclinical and clinical trial challenges are discussed, and some small molecule products already on the market are explored.