Advancements in salbutamol sulphate formulation: Spray-drying technique for the production of porous particles with enhanced properties for inhalation drug delivery

Abstract

AbstractA fast, simple and cost-effective technique has been used to produce spray-drying porous particles of salbutamol sulfate (SS) for inhalation drug delivery. The particles were produced using water as solvent and ammonium bicarbonate as pore-forming agent. A full factorial experimental design (24) with a central point was used to evaluate the influence of process parameters (drying air inlet temperature, atomization air volume flowrate, feed volume flowrate and the pore-forming agent concentration) on process yield, moisture content, densities and particle size. In addition, particle morphology, in-vitro aerosolization properties, stability and cytotoxicity of selected samples were studied. Within the experimental design parameters window, it was shown that the highest inlet temperature and pore-forming agent concentration were the factors that more affected the process yield and tap density values. Particles with the lowest tap densities values exhibited porous morphology. In addition, the pore-forming agent concentration proved to be the most significant variable affecting particle size. The highest pore-forming agent concentration, the largest particle size. The porous particles exhibit remarkable aerosolization performance, surpassing the performance of previously reported SS porous particles and a commercial formulation. These powders showed a high process yield and the absence of ammonium bicarbonate in the final product, as confirmed by FT-IR. Furthermore, the powders presented good stability even over long periods of time and did not exhibit cytotoxicity on the murine alveolar macrophage cell line RAW 264.7.Keywords: Porous particlessalbutamol sulfatespray dryingammonium bicarbonate Disclosure statementThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Additional informationFundingThe authors thank the financial support from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) [grant number: PIP 11220150100704CO] and Universidad Nacional del Sur (UNS) of Argentina [grant number: PGI 24M/163].