Development of dry powder Inhaler and nebulised nanoparticles formulations of chrysin for the potential treatment of asthma. Development of dry powder inhaler of chrysin and nebulised nanoemulsion combination of chrysin and budesonide; Evaluating the anti-inflammatory activity of the combination formulation of chrysin and budesonide for asthma

Abstract

Chrysin is a flavonoid that can be used as a medication for asthma and chronic obstructive pulmonary disease due to its anti-inflammatory activities. However, no studies have investigated the effectiveness of an inhaled formulation of chrysin on its own or in combination with corticosteroids. Therefore, this study aimed to assess the aerosol performance of chrysin formulations as well as the performance of combined formulations of chrysin and budesonide. Dry powder inhaler formulations were used first, where chrysin was processed using three different techniques, namely ball-milling, sonocrystallisation, and spray drying, to obtain a suitable particle size for inhalation. The highest fine particle fraction was 27% when the sonocrystallised samples were used. As the lung deposition was relatively low, budesonide was not added to the formulations. Next, liquid formulations of chrysin and budesonide were prepared in two concentrations using limonene and oleic acid as the oil phase. In a comparison of low and high drug concentrations of the formulations, the FPF of the formulations prepared with limonene ranged from 45% to 53.3% and from 49.3% to 53.9% for chrysin and budesonide, respectively; by contrast, the FPF of the formulations prepared with oleic acid oil ranged from 41% to 50.4% and from 46% to 53.3% for chrysin and budesonide, respectively. A genotoxicity study confirmed the safety of these combined formulations, and an anti-inflammatory study confirmed the potential for chrysin to be used with budesonide in a combined formulation; thus, chrysin’s anti-inflammatory efficacy can be improved and the required inhaled dose can be reduced.