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  • Title: In vitro evaluation of powders for inhalation: the effect of drug concentration on particle detachment.
    Author: Le VN, Hoang Thi TH, Robins E, Flament MP.
    Journal: Int J Pharm; 2012 Mar 15; 424(1-2):44-9. PubMed ID: 22207163.
    Abstract:
    Limited information on the effect of the drug concentration on the performance of powders for inhalation is currently published. The aim of this work was to study the influence of drug concentration on the adhesion between drug and carrier and on the drug detachment from the carrier. The study was done with formoterol fumarate and fluticasone propionate blended with lactose Lactohale 200. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and considering the whole blend as it is used in dry powder inhalers. Adhesion characteristics were evaluated by submitting the mixtures to a sieving action by air depression with an Alpine air-jet sieve. Aerodynamic evaluation of fine particle dose and emitted dose was obtained using a Twin Stage Impinger (TSI). Drug concentration of powder blends used in dry powder inhalers influenced adhesion, content uniformity and in vitro deposition of the drug. For the higher concentration of formoterol, it seemed that a lower quantity of drug adhered to the lactose. This was confirmed by the aerosolization assays done in the TSI. The fine particle fraction increased linearly with the formoterol concentration. A correlation was observed between adhesion characteristics and inertial impaction. In the case of fluticasone, the influence of the concentration was different. First, the fine particle fraction increased with the concentration and then decreased with a further increase of the fluticasone concentration. This could be explained by the lack of homogeneity when the fluticasone concentration was high because of agglomerates of pure drug which can not be redispersed, or by the physico-chemical characteristics of this drug.
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