Santoso Adi

Micro-particle corrugation, adhesion and inhalation aerosol efficiency.

Atomic force microscopy (AFM) was used to evaluate the particle adhesion and surface morphology of engineered particles for dry powder inhaler (DPI) respiratory therapy to gain a greater understanding of interparticle forces and the aerosolisation process. A series of spherical model drug particles of bovine serum albumin (BSA) was prepared with different degrees of surface corrugation. The particles were evaluated in terms of particle size (laser diffraction) and microscopic morphology (scanning electron microscopy). Conventional tapping mode AFM was used to evaluate the nanoscopic morphology and derive specific roughness parameters, while AFM colloid probe microscopy was used to directly measure the interaction of functionalised probes. The physical characterisation and AFM measurements were evaluated in terms of in vitro aerosolisation performance, using a conventional Rotahaler((R)) DPI and multistage liquid impinger. A direct relationship between the root mean square roughness, particle adhesion and in vitro aerosol performance (measured as fine particle fraction, FPF) was observed suggesting that as the degree of corrugation increased, particle adhesion was reduced which, resulted in a concomitant increase in FPF. This study demonstrates that AFM may be used to predict the aerosolisation performance micron sized particles for inhalation based on their morphological properties.

Scanning White-Light Interferometry as a Novel Technique to Quantify the Surface Roughness of Micron-Sized Particles for Inhalation

A novel approach of measuring the surface roughness of spherical and flat micron-sized drug particles using scanning white-light interferometry was applied to investigate the surface morphology of micron-sized active pharmaceutical ingredients (APIs) and excipient particles used for inhalation aerosols. Bovine serum albumin (BSA) and alpha-lactose monohydrate particles were chosen as model API and excipient particles, respectively. Both BSA and lactose particles were prepared with different degrees of surface corrugation using either controlled spray drying (four samples of BSA) or decantation (two samples of lactose). Particle size distributions were characterized by laser diffraction, and particles were imaged by scanning electron microscopy (SEM). Surface roughness of the BSA and lactose particles was quantified by white-light optical profilometry using vertical scanning interferometry (VSI) at full resolution using a 50x objective lens with 2.0x and 0.5x fields of view for BSA and lactose, respectively. Data were analyzed using Vision software (version 32, WYKO), and surface roughness values are expressed as root-mean-square roughness ( Rrms). Furthermore, data were compared to topographical measurements made using conventional atomic force microscopy. Analysis of the optical profilometry data showed significant variation in BSA roughness ranging from 18.58 +/- 3.80 nm to 110.90 +/- 13.16 nm for the smoothest and roughest BSA particles, respectively, and from 81.20 +/- 15.90 nm to 229.20 +/- 68.20 nm for decanted and normal lactose, respectively. The Rrms values were in good agreement with the AFM-derived values. The particle morphology was similar to SEM and AFM images. In conclusion, scanning white-light interferometry provides a useful complementary tool for rapid evaluation of surface morphology and roughness in particles used for dry powder inhalation formulation.

Impact angles as an alternative way to improve aerosolisation of powders for inhalation

This study aims to investigate the role of impact angles on the de-agglomeration performance of powders for inhalation. Agglomerates of a model drug mannitol were impacted at customized impaction throats containing two angles (15-75 degrees and 45-45 degrees) or a single angle (15 degrees, 45 degrees and 90 degrees) using various air flow rates. The mass fraction of fine particles <5microm in the aerosol (FPF(Loaded)) was measured by a liquid impinger coupled to a laser diffractometer. Results showed that for the two-angle throats, there existed an optimal angle (45 degrees) and air flow (120lmin(-1)) for the FPF(Loaded), resulting from a balance between improved de-agglomeration and enhanced throat deposition with increasing air flow. When the throat contained two equal angles of 45 degrees , most powder deposition occurred at the first angle, indicating that the first angle was likely to cause major de-agglomeration, while the second angle might act as a facilitator for further break-up, but the deposition was minimum as the fragment sizes and velocity at the second impaction were smaller. This hypothesis was supported by further studies using single-angle throats and numerical simulation (DEM-CFD). These findings imply the potential importance of using angular design features for multiple impactions to improve DPI performance.

Numerical Study of Effects of Powder Size and Polydispersity on the Dispersion of Fine Powders in a Cyclonic Flow

This paper investigated the dispersion of fine powder agglomerates in a cyclonic flow based on a combined computational fluid dynamics (CFD) and discrete element method (DEM) approach. Agglomerates formed with various particle sizes and polydispersities were dispersed at various airflow rates. The dispersion process was analysed in terms of flow and powder velocity, number of fragments and interactions on the agglomerates. It was observed that the dispersion was governed by two dominant but competitive interactions, i.e. particle‐particle cohesion and particle‐wall interaction. While the agglomerate of smaller particles is more difficult to disperse at a low flowrate with weak particle‐wall interaction, its dispersion is more efficient with increased flowrate and can generate larger fine particles than the agglomerate of larger particles. The effect of powder polydispersity is less significant to the dispersion efficiency, particular at a high airflow rate.