The effect of mixing on the dispersibility of adhesive mixtures for inhalation. Comparison of high shear and Turbula mixers.

This study investigates the effect of different mixers and the applicability of the mixing energy (ME) concept to dry powder formulations for inhalation. With the aim to step-wise build and expand this concept, adhesive mixtures of 2 % budesonide and lactose carrier were investigated, both with 1 % magnesium stearate (MgSt) added in a 'coating' step, and without, the latter referred to as 'naked' formulations. For high shear mixed formulations, the fine particle fraction (FPF) was found to increase with increasing ME up to 60 % and thereafter decreased, using the Novolizer device.

The match between adhesive mixture powder formulations for inhalation and the inhaler device.

The device or the formulation? Which one governs drug dispersibility from the inhaler? To address this question, three budesonide-containing reservoir DPIs: Novopulmon Novolizer®, Giona Easyhaler® and DuoResp Spiromax®, were analyzed using the Next Generation Impactor, NGI. Thereafter, the devices were carefully opened, emptied, and formulations were switched between devices. Finally, three 'prototype' formulations with carriers of different particle size were produced and tested in the Novolizer and Easyhaler devices.

Systematic Evaluation of the Effect of Formulation Variables on In Vitro Performance of Mometasone Furoate Suspension-Metered Dose Inhalers.

The therapeutic benefits of metered dose inhalers (MDIs) in pulmonary disorders are mainly driven by aerosol performance, which depends on formulation variables (drug and excipients), device design, and patient interactions. The present study provides a comprehensive investigation to better understand the effect of formulation variables on mometasone furoate (MF) suspension-based MDI product performance. The effects of MF particle size (volume median diameter; X) and excipient concentration (ethanol and oleic acid, cosolvent, and surfactant, respectively) on selected critical quality attributes (delivered dose (DD), fine particle dose of particles lesser than 5 µm (FPD < 5), ex-throat dose and median dissolution time (MDT)) were studied.

Laboratory Study Comparing Pharmacopeial Testing of Nebulizers with Evaluation Based on Nephele Mixing Inlet Methodology.

Determination of fine droplet dose with preparations for nebulization, currently deemed to be the metric most indicative of lung deposition and thus in vivo responses, involves combining two procedures following practice as described in the United States Pharmacopeia and the European Pharmacopeia. Delivered dose (DD) is established by simulating tidal breathing at the nebulizer, collecting the medication on a filter downstream of the nebulizer mouthpiece/facemask. Fine droplet fraction (FDF) is determined separately using a cooled cascade impactor operated at 15 L/min.

Orally inhaled drug performance testing for product development, registration, and quality control.

A DPI can be split into three different modules; device, formulation, process. These are developed in parallel, and together with the user they provide the performance of an inhalation product. During product development, these modules are evolving and changing, whereas the requirements on an inhalation product are always expressed in terms of the performance of the final commercial product.

Validation of a general in vitro approach for prediction of total lung deposition in healthy adults for pharmaceutical inhalation products.

Background: A validated method to predict lung deposition for inhaled medication from in vitro data is lacking in spite of many attempts to correlate in vitro and in vivo outcomes. By using an in vivo-like in vitro setup and analyzing inhalers from the same batches, both in vitro and in vivo, we wanted to create a situation where information from the in vitro and in vivo outcomes could be analyzed at the same time.

Method: Nine inhalation products containing either budesonide or AZD4818 were evaluated.

Mensuration and cleaning of the jets in Andersen cascade impactors.

Purpose: Fifty-three Andersen Cascade Impactors (404 stages) have been investigated using an automated visual stage mensuration technique. A cleaning method was suggested for stages with jets smaller than nominal diameters. The impact of nonapproved jet diameters on result parameters from particle size analysis was evaluated theoretically.

Dose delivery late in the breath can increase dry powder aerosol penetration into the lungs.

In addition to aerosol particle size and mode of inhalation, the time-point of dose delivery during inhalation may be an important factor governing the intrapulmonary distribution of aerosolized drug. To generate different intrapulmonary deposition patterns of a drug model aerosol, a device with the capability of delivering small amounts of technetium-99m-labeled lactose dry powder at pre-set time-points during inhalation was developed. A single dose of the radioaerosol was delivered after inhalation of 20% (A) or 70% (B) of the vital capacity inhaled through the device.