Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Mickey Socrates Ferdynand,Ali Nokhodchi

doi:10.1007/s13346-020-00707-6

Abstract

Although in dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.

Highlights

In dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations
It has been shown that particle interactions are of great importance in dry powder inhaler (DPI) formulations where the dispersion of the active pharmaceutical ingredient particles from carrier particles is critical for lung deposition [28]
In order to get 60–93 μm, the obtained samples were sieved and the mentioned fraction was used in DPI formulations

Summary

Introduction

In dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Β2-Adrenergic receptor agonists, such as salbutamol sulfate, act on the β2-adrenergic receptor to facilitate smooth muscle relaxation and dilation of bronchial passages [1] This enables patients suffering from a disease like that of asthma, which is a chronic inflammatory disease characterized by the obstruction of airflow due to bronchial airway constriction in response to a stimulus [2], the ability to breathe. This, in turn, results in less cohesive particles and a possible decrease in particle size due to the surfactant behavior of leucine, reducing the size of droplets produced during atomization [19], a better deposition

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