Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of “safer” antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative “superbugs,” every effort must be made to improve the clinical utility of the last-line polymyxins. Significance Statement Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.

Introduction: Dry powder inhalers (DPIs) are popular for pulmonary drug delivery. Various techniques have been employed to produce inhalation drug particles and improve the delivery efficiency of DPI formulations. Physical stability of these DPI formulations is critical to ensure the delivery of a reproducible dose to the airways over the shelf-life. Areas covered: This review focuses on the impact of solid-state stability on aerosolization performance of DPI drug particles manufactured by powder production approaches and particle-engineering techniques. It also highlights the different analytical tools that can be used to characterize the physical instability originating from production and storage. Expert opinion: A majority of the DPI literature focuses on the effects of physico-chemical properties such as size, morphology, and density on aerosolization. While little has been reported on the physical stability, particularly the stability of engineered drug particles for use in DPIs. Literature data have shown that different particle-engineering methods and storage conditions may cause physical instability of dry powders for inhalation and can significantly change the aerosol performance. A systematic examination of physical instability mechanisms in DPI formulations is necessary during formulation development in order to select the optimum formulation with satisfactory stability. In addition, the use of appropriate characterization tools is critical to detect and understand physical instability during the development of DPI formulations.