The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers (original) (raw)
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Pharmaceutics
Physico-chemical properties of lactose are key factors in adhesive mixtures used as dry powder inhaler (DPI). Despite the abundant literature on this topic, the effect of the polymorphism and pseudo-polymorphism of lactose has been seldom investigated and discussed although often lactose used in DPI is subjected to unit operations, which may alter its solid-state properties. Here, we studied the aerosolization performance of salbutamol sulphate (SS) or budesonide (BUD) formulations by investigating the effect of lactose pseudopolymorphism in ternary (coarse lactose/fine lactose/drug) and binary (coarse lactose/drug) mixtures. An improvement of the aerosolization performance of SS formulations with the increase of the amount of fine micronized lactose up to 30% (fine particle fraction (FPF) = 57%) was observed. Micronized lactose contained hygroscopic anhydrous α-lactose, which converted to α-lactose monohydrate at ambient conditions. This implied that the positive effect of fines on...
Journal of pharmaceutical sciences, 2011
It has been shown that dry powder inhaler (DPI) formulations typically achieve low fine particle fractions (poor performance). A commonly held theory is that this is due, at least in part, to low levels of detachment of drug from lactose during aerosolization as a result of strong adhesion of drug particles to the carrier surfaces. Therefore, the purpose of the present study is to overcome poor aerosolization performance of DPI formulation by modification of lactose particles. Lactose particles were crystallized by adding solution in water to different ratios of binary mixtures of ethanol—acetone. The results showed that modified lactose particles had exceptional aerosolization performance that makes them superior to commercial lactose particles. Morphology assessment showed that crystallized lactose particles were less elongated, more irregular in shape, and composed of smaller primary lactose particles compared with commercial lactose. Solid-state characterization showed that commercial lactose particles were α-lactose monohydrate, whereas crystallized lactose particles were a mixture of α-lactose monohydrate and β-lactose according to the ratio of ethanol—acetone used during crystallization process. The enhanced performance could be mainly due to rougher surface and/or higher amounts of fines compared with the lactose crystallized from pure ethanol or commercial lactose. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2665–2684, 2011
Journal of Pharmaceutical Sciences, 2001
The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63–90 μm) of α-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 μm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 μm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min−1 via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5–10 μm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5–15 μm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1424–1434, 2001