The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were recorded. Twenty-nine subjects (15 males) were enrolled. The inhalation maneuver had to be repeated by 19 subjects using the Aerolizer and 1 subject using a Novolizer. While eight (28%) subjects completely failed to inhale correctly via the Aerolizer (four were identified by the investigators immediately after inhalation, another four by bioanalytics later), all did it correctly via the Novolizer. The bioanalytical evaluation indicated two distinct serum peaks. The shapes of serum concentration-time profiles were more homogeneous after inhaling via the Novolizer than via the Aerolizer. After adjusting for the delivered dose the Cmax of formoterol predicting pulmonary absorption was higher after the Novolizer than after the Aerolizer, while the average AUC0-infinity levels indicating total systemic exposure were equivalent. There was no evidence for different pharmacodynamic behavior with respect to serum potassium and glucose profiles, vital signs, and ECG. The Novolizer yields higher pulmonary absorption of formoterol than the Aerolizer and equivalent safety profiles. Considering the lower variability of PK profiles and the higher proportion of correct inhalations, formoterol is more reliably inhaled via Novolizer.
[Show abstract][Hide abstract] ABSTRACT: Enhanced therapeutics are drug products derived from existing generic drugs that provide additional benefits to the patients and the healthcare system. Enhanced therapeutics are considered to be an important and relatively low risk source of innovation. Pulmonary drug delivery is the major delivery route to treat chronic respiratory diseases and has been proven as a potential delivery route for complex drugs that cannot be delivered orally. Development of dry powder inhalation systems targets the delivery of fine drug particles to the deep lung surface by a combination of drug formulation, primary packaging and a device, whereby each contributes to the overall performance. Various methodologies for the non-clinical and clinical performance testing of orally inhaled products have been proposed and applied with variable success. Regulatory pathways have been developed and applied since. Considerable efforts have been made during the past decade to understand and optimize pulmonary drug delivery including their efficient commercial manufacturing. Pulmonary drug delivery remains an area of future innovation in the effective treatment of pulmonary diseases as well as the systemic delivery of systemically active complex drugs.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2012; 48(1-2). DOI:10.1016/j.ejps.2012.10.021 · 3.35 Impact Factor
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