The influence of secondary processing on the structural relaxation dynamics of fluticasone propionate

This study investigated the structural relaxation of micronized fluticasone propionate (FP) under different lagering conditions and its influence on aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25°C, 75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60°C, 44% RH) for 14 days. Physicochemical, surface interfacial properties via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of the FP samples were characterized. Particle size, surface area, and rugosity suggested minimal morphological changes of the lagered FP samples, with the exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo surface reconstruction with a reduction in surface rugosity. LH and HH lagering reduced the levels of amorphous content over 90-day exposure, which influenced the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB analysis suggested that LH and HH lagering led to different interfacial interactions with lactose monohydrate but an increasing adhesive affinity with SX. HT lagering led to no detectable levels of the amorphous disorder, resulting in an increase in the adhesive interaction with lactose monohydrate. APSD analysis suggested that the fine particle mass of FP and SX was affected by the lagering of the FP. In conclusion, environmental conditions during the lagering of FP may have a profound effect on physicochemical and interfacial properties as well as product performance of binary and tertiary carrier-based DPI formulations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1208/s12249-014-0222-8) contains supplementary material, which is available to authorized users

From single excipients to dual excipient platforms in dry powder inhaler products

AbstractRecent years have seen a marked diversification of excipient based formulation strategies used for the development and commercialisation of dry powder inhaler (DPI) products. These innovative approaches not only provide benefits to patients and health care professionals through the availability of a wider range of therapeutic DPI products, but, importantly, also allow formulators to exploit the potential opportunities that excipients provide for the development of DPIs. Whilst many DPI products have, and continue to be developed using a single formulation excipient, the commercialisation of DPI products which contain the two excipients lactose monohydrate and magnesium stearate, namely the ‘dual excipient platform’ has recently been achieved. This article provides an overview of the background and current status of the development of such ‘dual excipient platform’ based DPI products

Formulated muco-regulatory agents in the airways of patients with cystic fibrosis

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Defining the Dosage Strength for Labelling of DPIs: Use, Limitations and Relevance of in-vitro Data

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Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy

Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1-5 µm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p < 0.05) reduce the elasticity and yield stress of CF sputum. The superior physical properties of UFH/L-leucine indicate this is the preferred formulation for development as an inhaled mucolytic