The on-line analysis of aerosol-delivered pharmaceuticals via single particle aerosol mass spectrometry.

The use of single particle aerosol mass spectrometry (SPAMS) was evaluated for the analysis of inhaled pharmaceuticals to determine the mass distribution of the individual active pharmaceutical ingredients (API) in both single ingredient and combination drug products. SPAMS is an analytical technique where the individual aerodynamic diameters and chemical compositions of many aerosol particles are determined in real-time. The analysis was performed using a Livermore Instruments SPAMS 3.0, which allowed the efficient analysis of aerosol particles with broad size distributions and can acquire data even under a very large particle load. Data similar to what would normally require roughly three days of experimentation and analysis was collected in a five minute period and analyzed automatically. The results were computed to be comparable to those returned by a typical Next Generation Impactor (NGI) particle size distribution experiment.

Preparation of porous microcrystalline cellulose pellets by freeze-drying: effects of wetting liquid and initial freezing conditions.

The effects of wetting liquid and initial freezing conditions on the pore volume and pore size distribution of freeze-dried microcrystalline cellulose (MCC) pellets were studied with mercury porosimetry. Freeze-drying was applied after extrusion/spheronization using two wetting liquids (water and water-isopropanol) and three initial freezing conditions (-30, 80, and -197 degrees C). Also, the effects of initial freezing were compared to those on pellets prepared with extraction of NaCl from Avicel(R)/NaCl pellets. Pellet porosity was found to increase with decreasing initial freezing temperature and the increase is greater for pellets made with water as wetting liquid. The mean pore diameter is greater for the extracted pellets, followed by nonextracted MCC pellets made with water and water-isopropanol. Also, the pore diameter is greater for freezing at -80 degrees C comparatively to that at -30 degrees C, while it is smaller for freezing at -197 degrees C. Narrower and more symmetrical pore size distributions were obtained with water-isopropanol at -197 degrees C. The higher porosity obtained with water alone and the smallest mean pore diameter and narrower distribution obtained with water-isopropanol may be due to the effects of H-bonding between isopropanol and water molecules on the nucleation and growth of ice crystals during the initial freezing.

Combined effects of wetting, drying, and microcrystalline cellulose type on the mechanical strength and disintegration of pellets.

Effects of wetting and drying conditions on micromeritic, mechanical and disintegration properties of microcrystalline cellulose (MCC) pellets were evaluated. Extrusion/spheronization and three drying methods (fluidized bed, microwaves, and freeze drying) were applied using two wetting liquids (water or water-isopropanol 60:40 w/w) and three MCC types: (standard, silicified, and modified). Additionally, the effects of drying method were compared on highly porous pellets prepared by the incorporation and extraction of pore former (NaCl). It was found that the drying method has the greatest effect on the pellet size and porosity followed by the wetting liquid. The modification of MCC resulted in reduced water retention ability, implying hornification, increased porosity, reduced resistance to deformation and tensile strength of pellets. The disintegration time also decreased markedly due to the modification but only in the low porosity range <37%. Silicification increased greatly the disintegration time of the low porosity pellets (<14%). Combination of water-isopropanol, freeze drying and modified MCC gave the greatest increase in pellet size and porosity. The increase in pellet porosity caused exponential reduction in the resistance to deformation, tensile strength and disintegration time, as expected. Compared to fluidized bed, the freeze drying resulted in 20-30% higher porosity for pellets prepared without pore former and 6% for those with pore former, indicating the possibility of preparing highly porous pellets by employing freeze drying.