R Kammelar | PubMed Health

PubMed2005

Effect of milling and sieving on functionality of dry powder inhalation products.

Alpha-lactose monohydrate is the standard excipient used as diluent or carrier in dry powder inhaler (DPI) formulations. Earlier studies have already revealed that raw materials for the production of inhalation grade lactose have to be carefully selected in order to avoid batch-to-batch variability. In the present study, the effect of milling and milling intensity on the flow properties and the physico-chemical characteristics of lactose crystals has been determined. The milled lactoses were then further processed by sieving to give lactose qualities with identical size distribution data, but different batch history (non-milled and milled at different conditions). These were then used to manufacture low concentration (0.25%) drug blends with the model drugs salbutamol sulphate (SBS) and beclometasonedipropionate (BDP); the blends were analysed with a Multistage Liquid Impinger (MLI) after delivery from an Easyhaler and an Aerolizer device. It could be shown that gentle milling already results in surface defects on the lactose crystal which are further enhanced by using a higher milling intensity. Produced fine lactose particles during the milling process strongly adhere to the lactose surface and cannot be removed by compressed air which is used for the particle sizing. By trend, a higher milling intensity resulted in higher fine particle fractions (FPF) with both devices. Also, SBS was found to generally give higher fine particle fractions than BDP, independent from the device used. In conclusion, lactose pre-treatment by gentle or strong milling affects the carrier surface and thereby the aerosolization properties of drug/lactose blends produced.

Aerosols↗

PubMed2004

Functionality testing of inhalation grade lactose.

Lactose monohydrate for inhalation is commonly produced by sieving out customer-specific size fractions of a crystallized bulk material of lactose. It was the aim of this study to investigate the influence of the raw material on the physico-chemical properties of the inhalation grade lactose and on the efficacy of powders for inhalation produced from these batches. The selected raw material lactose batches differed in the size distribution characteristics, the fines and the agglomerate content. These differences in the raw material could also be found to a smaller extent in the intermediate products and could not be completely levelled out in the final inhalation grade lactose. Efficiency testing was done using salbutamol sulphate in two different concentrations (drug-to-carrier ratio of 1:36 and 1:400) as a model drug; the powder blends were delivered using the Aerolizer and the Easyhaler device. With the high drug load, nearly no differences could be observed between both the delivery systems and the different produced lactose batches. The fine particle fraction (FPF) (%<5 microm) was on a high level of >39% in all cases. With the low drug load significant differences between the devices and the lactose batches were found. The FPF was distinctly reduced to 15-30%, with the Easyhaler generating a higher fraction of fine particles than the Aerolizer device. Although the observed differences between the lactose batches could not be linked to one specific physico-chemical parameter determined for the carrier, they led to the conclusion that the differences between the test batches of inhalation grade lactose especially manufactured for this study can affect the functionality of an inhalation powder. The effects are significantly smaller with high drug load formulations than using a low drug concentration.

Administration, Inhalation↗