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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. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to produce salbutamol sulfate (SS) as a model anti-asthmatic drug using high-gravity controlled precipitation (HGCP) through antisolvent crystallisation. An aqueous solution of SS was passed through a HGCP reactor with isopropanol as antisolvent to induce precipitation. Spray drying was employed to obtain dry powders. Scanning electron microscopy, X-ray powder diffraction (XRD), density measurement, thermal gravimetric analysis, and dynamic vapour sorption were carried out to characterise the powder physical properties. The aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60L/min. The HGCP SS particles were elongated with 0.1μm in width but varying length of several μm, which formed spherical agglomerates when spray dried. The particles showed the same XRD pattern and true density (1.3g/cm3) as the raw material, indicating that they belonged to the same crystalline form. However, the spray dried agglomerates had a much lower tapped density (0.1g/cm3) than the raw material (0.6g/cm3). Compared with the powder obtained by spray drying directly from an aqueous solution, the SS powders obtained from HGCP were much less hygroscopic (0.6% versus 10% water uptake at 90% RH). The in vitro aerosol performance showed a fine particle fraction FPFloaded and FPFemitted up to 54.5±4.9% and 71.3±10.0%, respectively. In conclusion, SS powder with suitable physical and aerosol properties can be obtained through antisolvent HGCP followed by spray drying. [Copyright &y& Elsevier]

The influence of processing on the performance of carrier material used in dry powder inhalers was investigated. α-Lactose monohydrate crystals were processed by ball milling for cumulative time durations and their properties evaluated. As expected, milling reduced the median particle diameter while increasing fine particulate (<10 µm) and amorphous levels. Recrystallization of these partially amorphous samples resulted in a reduction in fines, elimination of amorphous material with little change in median diameter. To study the effects of processing on aerosolization performance, blends of lactose monohydrate with a model drug (nedocromil sodium trihydrate), were evaluated using an in vitro multistage liquid impinger (MSLI) model. In general, milling and storage of the carriers at high humidity (prior to blending) had a significant (ANOVA, p < 0.05) effect on the fine particle fractions (FPF; <6.8 µm). These effects were attributed predominantly to the fines content, showing a strong correlation between increased fines and FPF (R2 = 0.974 and 0.982 for milled and recrystallized samples, respectively). However, this relationship only existed up to 15% fines concentration, after which agglomerate-carrier segregation was observed and FPF decreased significantly. These results suggest that, after processing, high-dose drug formulation performance is dominated by the presence of fines. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1331–1341, 2007 [ABSTRACT FROM AUTHOR]

Abstract: Fine sodium chloride particles are of pharmaceutical interest in aerosol delivery for diagnosis of asthma and bronchial related disorders. In this paper, stable NaCl particles with size ranging from approximately to sub-micron range were achieved by sonocrystallisation. The effects of sonocrystallisation temperature, ultrasonic power output and salt concentration were investigated in the ranges of , 22–60W and 8–34g/100g water, respectively, under a fixed ultrasonic frequency of 20kHz. Size and morphology characterisation of particles were undertaken using laser diffraction and scanning electron microscopy. Optimally prepared particles were spray dried followed by in vitro impaction test for inhalation efficiency determination using an . Optimal conditions of temperature ), ultrasonic power output and salt concentration water) exist that reduced the size of the crystals to the sub-micron scale. Spray drying increased the size of the prepared particles and altered the cubic shape to more rounded morphology. The fine particle fraction (based on recovery) was improved from approximately 12 to 34% when dispersion air flow rate was increased from 60 to 120L/min. Sonocrystallisation represents an effective method for the preparation of NaCl particles suitable for pharmaceutical inhalation. The main advantage of this method is that it is rapid, simple and produces small crystal NaCl particles suitable for inhalation. [Copyright &y& Elsevier]