A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Preparation of berberine hydrochloride dry powder inhalation and its effect on Staphylococcus aureus pneumonia / 中草药

Objective: To prepare berberine hydrochloride dry powder inhalation, and investigate its pharmacological effect on Staphylococcus aureus pneumonia after pulmonary administration. Methods: Berberine hydrochloride dry powder by spray drying and the experimental conditions was optimized by orthogonal experiment. The lung deposition, fluidity and appearance were characterized. The pharmacodynamic effects of the preparations on S. aureus pneumonia were performed with SD rats. Results: A berberine hydrochloride dry powder was prepared at an inlet temperature of 130 ℃ with a gas volume flow of 610 L/h and a feed volume flow of 3 mL/min. The berberine hydrochloride dry powder had a lung deposition rate (FPF) of 76.4% and an aerodynamic diameter of 4.61 μm. The stability index (SI) ≈ 1, the aeration energy ratio (AR) = 1.76 > 1, and the inflation energy (AE10) = 2.1 mJ < 10 mJ. Through the pharmacodynamic evaluation of S. aureus, we can know that the berberine hydrochloride dry powder inhalation effectively improved the pathological state of pneumonia rats, and significantly reduced (P < 0.05) the number of WBC, neutrophils, and the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) in pneumonia rats. Conclusion: Berberine hydrochloride dry powder inhalation can directly reach the lesion site through pulmonary administration, so it has significant therapeutic effect on S. aureus pneumonia.