Amino acid-modified spray-dried powders with enhanced aerosolisation properties for pulmonary drug delivery

In this study, the amino acids arginine, aspartic acid, leucine, phenylalanine and threonine were investigated as 'dispersibility enhancers' in spray-dried powders for inhalation. Parameters such as spray-dried yield, tapped density, and Carr's Index were not predictive of aerosolisation performance. In addition, whilst the majority of amino acid-modified powders displayed suitable particle size distribution for pulmonary administration and potentially favourable low moisture content, in vitro particle deposition was only enhanced for the leucine-modified powder. In summary, leucine can be used to enhance the dispersibility and aerosolisation properties of spray-dried powders for pulmonary drug delivery. © 2007 Elsevier B.V. All rights reserved.

Spray-dried powders for pulmonary drug delivery

Powders for inhalation are traditionally prepared using a destructive micronization process such as jet milling to reduce the particle size of the drug to 2-5 μm. The resultant particles are typically highly cohesive and display poor aerosolization properties, necessitating the addition of a coarse carrier particle to the micronized drug to improve powder flowability. Spray-drying technology offers an alternative, constructive particle production technique to the traditional destructive approach, which may be particularly useful when processing biotechnology products that could be adversely affected by high-energy micronization processes. Advantages of spray drying include the ability to incorporate a wide range of excipients into the spray-drying feedstock, which could modify the aerosolization and stability characterizations of the resultant powders, as well as modify the drug release and absorption profiles following inhalation. This review discusses some of the reasons why pulmonary drug delivery is becoming an increasingly popular route of administration and describes the various investigations that have been undertaken in the preparation of spray-dried powders for pulmonary drug delivery. © 2007 by Begell House, Inc.

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients. METHODS Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16–28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h−1) = 11.4 × (WT/70.0)0.75 and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h−1 and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h. CONCLUSIONS The range of estimated CL/F in the study population was 0.67–7.38 l h−1. The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.