Understanding the impact of L-leucine on physical stability and aerosolization of spray-dried protein powder formulations containing trehalose.

There is a growing interest in developing solid formulations for protein products due to enhanced physico-chemical stability. Spray drying is a widely used process for the manufacturing of solid-state protein therapeutics for pulmonary delivery. Stabilizers such as trehalose are commonly used and play a critical role in preventing protein degradation during the process of spray drying and upon storage.

Particle surface coating for dry powder inhaler formulations.

Introduction: The development of dry powder inhalers (DPIs) is challenging due to the need for micronized particles to achieve lung delivery. The high specific surface area of micronized particles renders them cohesive and adhesive. Addition of certain excipients like magnesium stearate has been reported to coat the particles and improve the aerosolization in the carrier-based DPI.

Impact of Co-Spray Drying with Leucine or Trileucine on Aerosol Performance, In Vitro Dissolution, and Cellular Uptake of Colistin Powder Formulations for Inhalation.

: Surface enrichment of hydrophobic excipients via spray drying has been demonstrated as an efficient way to protect the dry powder inhaler formulations against moisture-induced deterioration in aerosol performance. However, the impact of such surface enrichment on dissolution and cellular uptake is less investigated, which can affect the safety and efficacy of dry powder inhalers (DPIs). : In the present work, hygroscopic colistin was coated with leucine or trileucine, at different weight ratios during spray drying.

Recent advances in drying and development of solid formulations for stable mRNA and siRNA lipid nanoparticles.

Current RNA lipid nanoparticle (LNP) based products are typically liquid formulations that require ultra-cold storage temperatures for stability. To address this limitation, recent efforts have focused on enhancing stability and enabling room temperature storage by converting these formulations into solid forms through drying processes such as lyophilization, spray drying, and spray-freeze drying. Nevertheless, the drying process itself can influence the stability of RNA/LNP formulations.

Effects of buffers on spray-freeze-dried/lyophilized high concentration protein formulations.

Solid-state protein formulations are known to exhibit enhanced storage stability compared to their liquid dosage form counterparts. pH is one of the factors affecting the stability of protein formulations. The pH of protein formulations in the solution could be influenced by the buffer used, directly impacting their solid-state stability.

Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine.

We have recently shown that the volatile anesthetics isoflurane and sevoflurane acutely enhance the brain uptake of the hydrophilic markers sucrose and mannitol about two-fold from an awake condition, while the combined injection of the anesthetic agents ketamine and xylazine has no effect. The present study investigated two small-molecule hydrophilic drugs with potential neurotoxicity, the antibiotic agents ceftazidime and gentamicin. Transport studies using an in vitro blood-brain barrier (BBB) model, a monolayer of induced pluripotent stem cell-derived human brain microvascular endothelial cells seeded on Transwells, and LC-MS/MS analysis demonstrated the low permeability of both drugs in the range of sucrose, with permeability coefficients of 6.