Herbert Chiou

Influence of Mouthpiece Geometry on the Aerosol Delivery Performance of a Dry Powder Inhaler

PurposeTo investigate the influence of mouthpiece geometry on the amount of throat deposition and device retention produced using a dry powder inhaler (Aerolizer®), along with the subsequent effect on the overall inhaler performance.Materials and MethodsComputational Fluid Dynamics analysis of the flowfield generated in the Aerolizer® with various modified mouthpiece geometries (including cylindrical, conical and oval designs) was used in conjunction with experimental dispersions of mannitol powder using a multi-stage liquid impinger to determine how the overall inhaler performance varied as the mouthpiece geometry was modified.ResultsGeometry of the inhaler mouthpiece had no effect on device retention or the inhaler dispersion performance. In contrast, the mouthpiece geometry strongly affected the amount of throat deposition by controlling the axial component of the exit air flow velocity. The radial motion of the emitted aerosol jet was found to have little effect on throat deposition in representative mouth–throat models. Despite the reduced throat deposition, there was no difference in the overall inhaler performance.ConclusionsFor cases where low throat deposition is a key design parameter, this study demonstrates that the amount of throat deposition can be reduced by making minor modifications to the inhaler mouthpiece design.

The Use of Organic Vapor Sorption to Determine Low Levels of Amorphous Content in Processed Pharmaceutical Powders

ABSTRACT Organic dynamic vapor sorption (organic-DVS) was used to characterize amorphous content in known amorphous-crystalline mixtures of lactose and salbutamol sulfate. N-octane was chosen as an apolar probe and measurements were carried out by exposing mixtures of each sample to partial pressures 0–90% p/p0. A linear relationship between amorphous content and n-octane partial pressure was observed for both lactose and salbutamol sulfate with R2 values of 0.992 and 0.999, respectively. In addition, the influence of sequential mechanical processing in a ball mill on the amorphous content in crystalline lactose was investigated. Cumulative milling times resulted in an exponential increase in amorphous content (using the linear relationship obtained for lactose), with a maximum amorphous content of 14% being induced after 60 min milling. In comparison, analysis of the 60 min mill time samples after exposure to 85% relative humidity suggested 0.00% amorphous content.

Characterisation and aerosolisation of mannitol particles produced via confined liquid impinging jets.

Mannitol particles, produced by spray drying (SD), have been used commercially (Aridol) in bronchial provocation test. In this study, we propose an alternative method to produce inhalable mannitol powders. The elongated mannitol particles (number median length 4.0microm, and axial ratio of 3.5) were prepared using a confined liquid impinging jets (CLIJs) followed by jet milling (JM). Spray dried and jet milled raw mannitol particles were compared in an attempt to assess the performance of the particles produced by the new method. Aerosol performance of the three different powders (CLIJ, SD, and JM) was relatively poor (fine particle fraction or FPF(loaded) below 15%) when dispersed by the Rotahaler. Dispersion through the Aeroliser led to better aerosol performance of the CLIJ mannitol (FPF(loaded) 20.3%), which is worse than the JM (FPF(loaded) 30.3%) and SD mannitol particles (FPF(loaded) 45.7%) at 60 L/min, but comparable (FPF(loaded) 40.0%) with those of the JM (FPF(loaded) 40.7%) and SD (FPF(loaded) 45.5%) powders at 100L/min. Hence, the optimum use of these elongated mannitol particles can be achieved at increased air flow with a more efficient inhaler. In addition to crystallinity, morphology, and particle size distribution, the surface energies of these powders were measured to explain the differences in aerosol performance. A major advantage of using the CLIJ method is that it can be scaled up with a good yield as the precipitate can be largely collected and recovered on a filter, compared with spray drying which has a low collection efficiency for fine particles below 2microm.

Evaluation on the Use of Confined Liquid Impinging Jets for the Synthesis of Nanodrug Particles

Most pharmaceutical compounds can benefit from being produced with a small particle size to enhance processing or therapeutic performance. Confined liquid impinging jets (CLIJ) were employed in this study to evaluate the feasibility and limitations in the production of nanodrugs (i.e., particle size in the nanorange). Four drugs from different pharmaceutical classes and water solubilities—salbutamol sulfate, mannitol, ibuprofen, and cyclosporine—were examined. Particles of salbutamol sulfate and cyclosporine with diameters of approximately 300 nm were successfully achieved. The use of CLIJ thus shows potential in the production of nanopharmaceuticals for certain compounds.

The 15th International Society of Aerosols in Medicine Congress. Perth, Australia, 14-18 March 2005.

This international meeting brought together ∼ 250 delegates from the pharmaceutical industry, academia, hospitals and government agencies, to discuss the latest research and development on areas related to inhalation aerosols. Fundamental science and applied research encompassing both the biological and physicochemical aspects were presented. There was a wide range of topics covered, from immune modulation to pharmaceutical regulatory issues, including aerosol clearance; industry innovations; aerosols and in utero effects; technical advances in imaging; inhalation catastrophes; as well as recent advances and future directions in aerosol delivery systems. This biennial congress has provided an excellent forum for stimulating fruitful discussion of aerosols in medicine.