Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray drying technique

Abstract

BackgroundThe aim of this work was to develop dry powder inhaler (DPI) formulations of salbutamol sulfate (SS) by the aid of solid lipid microparticles (SLmPs), composed of biocompatible phospholipids or cholesterol.MethodsThe SLmPs were prepared by using two different solvent systems (ethanol and water-ethanol) and lipid carriers (dipalmitoylphosphatidylcholine (DPPC) and cholesterol) with/without L-leucine in the spray drying process. The spray-dried microparticles were physically-mixed with coarse lactose monohydrate in order to make our final DPI formulations and were investigated in terms of physical characteristics as well as in vitro drug release profile and aerosolization behavior.ResultsWe observed significant differences in the sizes, morphologies, and in vitro pulmonary depositions between the formulations. In particular, the SS-containing SLmPs prepared with water-ethanol (30:70 v/v) solution of DPPC and L-leucine which had then been blended with coarse lactose (1:9 w/w) exhibited the highest emitted dose (87.9%) and fine particle fraction (42.7%) among the formulations. In vitro drug release study indicated that despite of having a significant initial burst release for both cholesterol and DPPC-based microparticles, the remained drug released more slowly than the pure drug.ConclusionThis study demonstrated the potential of using lipid carriers as well as L-leucine in DPI formulations of SS to improve its aerosolization behavior and retard the release profile of the drug.

Inhalable Fucoidan Microparticles Combining Two Antitubercular Drugs with Potential Application in Pulmonary Tuberculosis Therapy

“…The wrinkled surface can also be thought of as a result of the drying process, in which the removal of ethanol from the microparticles’ surface occurs faster than water evaporation. The higher volatility of ethanol induces the formation of a primary shell that collapses as the water content in the core evaporates [23].…”

“…The adequate flowability is possibly a result of the wrinkled surfaces observed in the produced microparticles. Surface irregularities can reduce the cohesion forces between particles that lead to agglomeration, enhancing powder dispersibility, as well as improving the respirable fraction of the formulation [23,29]. This aspect is crucial when a lactose carrier is not included in the formulation, and spray-dried microparticles are aerosolised alone [16].…”

Effect of Lipidic Excipients on the Particle Properties and Aerosol Performance of High Drug Load Spray Dried Particles for Inhalation

“…However, on changing to water-ethanol (30−70% v/v) co-solvent system the particles were wrinkled. 26 Thus, the choice of lipids, spray drying parameters, spray drying solvent, and drug loading all have the potential to impact aerosol performance for phospholipid-based formulations.…”

Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation

“…In addition to controlled drug release, these formulations possess adequate aerodynamic properties [7]. The development of inhalable SLM powders has been described in literature [7][8][9][10][11][12][13][14][15][16][17][18][19][20]; however, the methods/apparatuses for their aerodynamic assessment, as the most important in vitro test, have been rather diverse, e.g., multistage liquid impinger (MSLI) [7][8][9][10][11]13,15,18], Andersen cascade impactor (ACI) [8,9,12], twin stage impinger (TSI) [19], fast screening impactor (FSI) [20] and next generation impactor (NGI) [20].…”