A simple method for assaying colistimethate sodium in pharmaceutical aerosol samples using high performance liquid chromatography.

A rapid and simple reversed-phase high performance liquid chromatography (HPLC) method for the quantitation of colistimethate sodium in pharmaceutical formulations has been developed. The chromatographic separation was performed using a Phenomenex Kinetex XB-C18 column with gradient elution using a mobile phase containing acetonitrile and 32mM sodium sulphate. Quantitation is based on the sum of the areas of two prominent peaks in the chromatogram, which produces a total peak area that is stable for 120 sample injections. The HPLC method was validated over the range 0.05-7mg/mL, and was shown to be suitable for the analysis of aerosolised pharmaceuticals in terms of aerosol output onto filter and for the analysis of samples from a cascade impactor, which is used for the determination of aerosol particle size.

Drug Delivery in Asthmatic Children Following Coordinated and Uncoordinated Inhalation Maneuvers: A Randomized Crossover Trial.

BACKGROUND: Valved holding chambers (VHCs) are used in children to deliver pressurized metered dose inhalers (pMDI). In vitro data suggest that uncoordinated use decreases the amount of drug available for inhalation. We hypothesize that in an ex vivo study, the coordinated maneuver will deliver more drug than the uncoordinated one. PATIENTS AND METHODS: Thirty-two clinically stable asthmatic children, ages 5-8 years, completed the study. An aerosol filter was interposed between a small-volume nonelectrostatic VHC and a mouthpiece to capture the drug emitted by one puff of Flovent® 220 mcg during tidal breathing. Inhalation and actuation parameters were measured by an electronic monitor, and the number of breaths required to empty the VHC was calculated. Subjects completed three coordinated and three uncoordinated (actuation at the beginning of inhalation and exhalation, respectively) runs in random order. Drug content from the filter and VHC was measured by high-performance liquid chromatography and expressed as percentage of emitted dose. RESULTS: [mean (99% confidence interval)] Filter dose was higher during coordinated technique 46% (43%-50%) than during uncoordinated technique 41% (37%-44%) (p < 0.001). Peak inspiratory flow and tidal volume were 23.2 L/min (21.3-25.1 L/min) and 281 mL (251-311 mL), respectively. Subjects required three breaths to empty the VHC in 96% of the tests. CONCLUSIONS: Actuating the pMDI into a small-volume nonelectrostatic VHC during exhalation reduced by 11% the amount of fluticasone captured at the exit of the VHC. Asthmatic children (5-8 years old) need three or less breaths to empty the small-volume VHC (NCT01714063).

Factors to consider when selecting a nebulizer for a new inhaled drug product development program.

INTRODUCTION: Nebulizers are a common device choice for use when developing a new drug product, but the range of nebulizer devices available can make it difficult to select the right device. Increasingly, companies are only able to promote a drug with the device that was used during the development program; therefore, choosing the best device at an early stage is important in order to achieve commercial success. Selecting a device that is inappropriate for the intended drug can result in poor drug delivery from the nebulizer to the patient, which would have obvious implications for the development program. As device performance varies, it is important to ensure that the most appropriate device is chosen for the intended drug to ensure optimal drug delivery to the patient population. AREAS COVERED: In this review, the types of nebulizer devices available are highlighted, and the factors that should be taken into consideration when selecting the most appropriate device for a new drug are discussed. The review is broadly divided into drug, device, patient and trial characteristics. EXPERT OPINION: Efficient nebulizer devices that combine electronic monitoring capabilities as a form of telehealth are likely to provide superior drug delivery to patients and accurate clinical trial data. Their use in adaptive clinical trials may help to vastly reduce the time and costs associated with achieving drug approval.

In vitro characterization of the I-neb Adaptive Aerosol Delivery (AAD) system.

The in vitro characterization of device-related parameters such as the rate of aerosol output, total aerosol output, particle size, and fine particle fraction, is essential when assessing the potential performance of a nebulizer or making comparisons with other nebulizers as they are indicative of potential clinical performance. This article reviews a number of in vitro studies designed to characterize the I-neb Adaptive Aerosol Delivery (AAD) System in terms of drug delivery (particle size, residual, reproducibility, precise dose delivery, dose equivalence), in terms of drug-related performance (osmolality, surface tension, viscosity), and in terms of nebulizer orientation during operation. The results of the in vitro tests of drug delivery indicate that the I-neb AAD System is suitable for delivery of aqueous solutions by nebulization. The evaluation of equivalent doses between the I-neb AAD System (metered dose) and a conventional jet nebulizer (delivered dose), demonstrates that the amount of drug required to deliver the same dose is up to five times less with the I-neb AAD System due to the low residual and controlled drug delivery. The lack of change in osmolality during nebulization might be of importance as it presents an opportunity for delivery of drugs to patients with hyperreactive airways, or where a specific tonicity of the formulation is required. The physicochemical characteristics (surface tension, viscosity) of a number of drugs delivered with the I-neb AAD System highlights some of the demands created by existing and new drug formulations. Finally, the study of the impact of nebulizer orientation shows how important it is to also consider how the nebulizer will actually be physically used by the patient rather than solely under standard conditions used within the laboratory.