Effect of the API on the Performace of Adhesive Mixtures for Inhalation

Sammanfattning

Dry powder inhalers (DPIs) are widely used to treat respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The performance of DPI formulations is influenced by the properties of the active pharmaceutical ingredient (API), but systematic comparative studies of different APIs under the same processing conditions remain limited. This study investigated the effects of different APIs on the performance of lactose-based inhalation binder mixtures. In this study, five APIs (budesonide (AstraZeneca and Teva), indacaterol maleate, salbuta-mol sulphate, and salmeterol xinafoate) were mixed with lactose carrier particles using a high-shear mixing method. Some formulations were also prepared using a low-shear mixing method. Homogeneity, bulk density, and fine particle fraction (FPF) of the formulations were assessed using a next-generation impactor (NGI), and hygroscopicity was assessed using iso-thermal microcalorimetry. Most formulations exhibited acceptable homogeneity, but salmeterol xinafoate showed high-er variability under high-shear conditions and salbutamol sulphate under low-shear condi-tions. All binary mixtures had higher bulk densities than pure lactose carrier. Significant dif-ferences in DPI performance were observed between different APIs. Salbutamol sulphate and indacaterol maleate had the highest effective FPF, while prolonged high-shear mixing gener-ally decreased FPF. Conversely, low-shear mixing increased FPF with increasing mixing time. Isothermal micro-calorimetry measurements showed that most formulations were sta-ble under humid conditions, while salbutamol sulphate showed slight signs of recrystalliza-tion. Previous studies have demonstrated an empirical relationship between the FPF of DPI formu-lations and the mixing energy (ME). This study further evaluated the applicability of this model to different API formulations. The results showed that introducing a constant C into the original empirical model improved the fit between the model and experimental FPF data for some APIs, suggesting that this constant may be related to the properties of the API itself. These results indicate that even when formulation composition and processing conditions remain constant, the properties of the API can affect the performance of inhaled adhesive mixtures. These findings provide useful guidance for the design and optimization of DPI formulations.