Physical characteristics and aerosolization performance of insulin dry powders for inhalation prepared by a spray drying method

Abstract

The objective of this study was to investigate the influence of formulation excipients on the physical characteristics and aerosolization performance of insulin dry powders for inhalation. Insulin dry powders were prepared by a spray drying technique using excipients such as sugars (trehalose, lactose and dextran), mannitol and amino acids (L-leucine, glycine and threonine). High performance liquid chromatography and the mouse blood glucose method were used for determination of the insulin content. The powder properties were determined and compared by scanning electron microscopy, thermo-gravimetric analysis and size distribution analysis by a time-of-flight technique. The in-vitro aerosolization behaviour of the powders was assessed with an Aerolizer inhaler using a twin-stage impinger. Powder yield and moisture absorption were also determined. Results showed that there was no noticeable change in insulin content in any of the formulations by both assay methods. All powders were highly wrinkled, with median aerodynamic diameters of 2-4 microm, and consequently suitable for pulmonary administration. The tapped density was reduced dramatically when glycine was added. The powders containing mannitol, with or without L-leucine, were less sensitive to moisture. The highest respirable fraction of 67.3 +/- 1.3% was obtained with the formulation containing L-leucine, in contrast to formulations containing glycine and threonine, which had a respirable fraction of 11.2 +/- 3.9% and 23.5 +/- 2.5%, respectively. In addition, powders with good physical properties were achieved by the combination of insulin and trehalose. This study suggests that L-leucine could be used to enhance the aerosolization behaviour of the insulin dry powders for inhalation, and trehalose could potentially be used as an excipient in the formulations.

Nanocomposite microparticles (nCmP) for the delivery of tacrolimus in the treatment of pulmonary arterial hypertension

“…The formation of nanoparticle shells during spray drying determines the geometric size of nCmP. As the drying proceeds, the remaining water keeps evaporating from the droplet center, resulting in hollow particles that tend to shrink (39, 40). The number average geometric diameter of the TAC nCmP system was 2.13 ± 0.52 µm, as determined by ImageJ analysis.…”

Lactose characteristics and the generation of the aerosol

“…It is interesting to note that lactose is often used as a bulking agent and stabilising adjuvant in spray-dried formulations of sensitive drugs, peptides and proteins to provide some protection during the manufacturing process against shear forces and increased temperatures in particular [200][201][202][203][204][205]. The structure and activity of dried proteins are protected by hydrogen bonding with lactose, which enables the production of stable particles of a size suitable for inhalation and allows a rapid release of the drug in the lung.…”

Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization

“…1,15 Particles formed from spray drying can be spherical, 16 porous, 17 wrinkled 16,18 and dimpled, 19,20 each of which are proposed to be optimized for improved aerosolization performance. 21 Excipients and spray drying parameters can be manipulated to control the particle size, morphology and surface energy. 22 Aerosol performance of powders is strongly affected by the surface energy 23 as inter-particulate forces are dependent on the surface energy of the particles.…”