Atualmente, vários medicamentos estão sendo usados de forma sistêmica para o tratamento da Síndrome Respiratória Aguda Grave Coronavírus 2 (SARS-CoV-2). No entanto, poucos estudos discutem a possibilidade de utilizar a via inalatória para esse fim. Os nebulizadores pneumáticos e ultrassônicos são cada vez mais utilizados devido à facilidade com que esses meios entregam os medicamentos por meio de uma suspensão em aerossol para dispensar os medicamentos de forma localizada no trato respiratório, proporcionando maior eficiência de absorção. Este estudo tem como objetivo caracterizar os diâmetros das gotas por faixas de "partículas respiráveis" geradas por nebulizadores comercializados no Brasil (2 pneumáticos e 1 ultrassônico), utilizando a técnica de incidência laminar direta (ILD). Além disso, discutir o uso de medicamentos por inalação com base nas propriedades físico-químicas e farmacológicas. No procedimento de nebulização, as imagens das gotículas aerodinâmicas dispersas foram capturadas usando a técnica ILD. Foram elaborados histogramas de distribuição do diâmetro das gotas, enfatizando a faixa de gotas com diâmetros entre 1,0 a 5,0 µm. Os resultados atestaram que cada nebulizador tem sua própria característica de entregar a suspensão aerodinâmica no processo de nebulização. Neste estudo, o ILD representa uma alternativa viável para caracterização das gotículas aero dispersas, de fármacos usados mundialmente para o tratamento de sinais e sintomas da SARS-CoV-2.

Introduction: Optical microscope images can be useful to evaluate nebulizers considering the size of droplets produced by these devices. From this perspective, the proposed method was compared to the classic concept of Mass Median Aerodynamic Diameter (MMAD) for the ideal droplet size between 0.5-5.5 µm. Methods: We tested a sample of five home nebulizers sold on the Brazilian market. A high-speed camera coupled to a microscope obtained images of the droplets during the nebulization process, which allowed us to characterize the diameter of the aero-dispersed droplets. The Count Median Aerodynamic Diameter (CMAD) was used as measurement parameter. Results: The images obtained during the nebulization process with the five different nebulizers provided data to determine the frequency distribution of the aero-dispersed droplet population. Successive images were obtained in the range of 2.0s to evaluate the dynamic behavior of the droplets. The generated data also allowed the elaboration of histograms emphasizing the ideal diameter range of droplets between 0.5 and 5.5 μm. Conclusion: The Direct Laminar Incidence (DLI) model using digital image processing technique allowed the characterization of respirable particles. This model proposes the creation of a range of optimum absorption of the droplets by the respiratory tract. Although there is a technical limitation in the direct acquisition of images due to the depth of focus, presenting an error of 9.3%, the described method provides consistent results when compared to other droplets characterization techniques. Thus, the authors believe that Direct Laminar Incidence (DLI) is a viable method to assess the performance of nebulizers despite the requirement of adjustments and possible improvements required to minimize measurement errors.

The Microfluidics emerged at the end of the 1970’s decade as a result of the use of the technology responsible for the development of micro electromechanical systems (MEMS) that utilized the infrastructure and well-established manufacturing techniques for microelectronics. Initially, silicon was used as substrate for the manufacture of micros systems, however in the last decades it has been replaced by other materials like glass, polymers and ceramic. Currently the most widely used technique in the fabrication of Microfluidic devices is the microlithography. However, besides having a high operating cost, this manufacturing technique requires additional procedures for adapting the interfaces of micro scale to macro scale (e.g. connections), which makes it even more complex. 3D printing technique used in the fabrication of microfluidic devices can overcome these difficulties and become a viable alternative, since it has the ability to fabricate devices in a single printing step. In addition to removing the need for additional procedures relating to adaptations of the interfaces, this technique allows to produce devices with circular sections channels. In this work microfluidic devices are manufactured according to the technique of 3D printing. They were tested for the production of monodisperse microbubbles aimed to clinical applications. The results proved the efficiency of the devices in the generation of microbubbles with the percentage variation rate of 0.4% and average diameter of 73.7 μm.

Currently, several drugs are being used systemically to treat Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, few studies discuss the possibility of using the inhalation route for this treatment. Pneumatic and ultrasonic nebulizers are increasingly used due to the ease with which these media deliver drugs through an aerosol suspension to deliver drugs in a localized manner in the respiratory tract, providing greater efficiency of absorption. This study aims to characterize the droplet diameters by bands of "breathable particles" generated by nebulizers commercialized in Brazil (2 pneumatic and 1 ultrasonic), using the direct laminar incidence (DLI) technique. In addition, to discuss the use of drugs by inhalation based on the physicochemical and pharmacology properties. In the nebulization procedure, the images of the dispersed aero droplets were captured using the DLI technique. Droplet diameter distribution histograms were elaborated, emphasizing the range of droplets with diameters between 1.0 to 5.0 µm. The results attested that each nebulizer has its own characteristic of delivering the aerodynamic suspension in the nebulization process. In this study, DLI represents a viable alternative for characterization of the aero dispersed droplets, of drugs used worldwide to treat SARS-CoV-2 signs and symptoms.

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