1. Results and Discussion
Influence of two different devices in formulation’s aerodynamic performance
Nélio Drumond, Ana Costa, André Sá Couto and Helena Cabral-Marques
Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa, Portugal.
A7BXH-F5Z6G-7KZZ7-8784W-7SC7G
Introduction
Lung diseases are more effectively treated with local therapy when compared to systemic delivery. Unique features such as surface area, permeability and blood supply, make the pulmonary route an attractive and non-invasive way for drug delivery.
Standard therapy consists of β-adrenergic agonists and corticosteroids inhalers. Although effective, corticosteroids are poorly water soluble.
Cyclodextrins (CyDs), molecular entities used as pharmaceutical vehicles, may be used to overcome this limitations.
Dry powder inhalers (DPIs) represent an effective drug delivery platform, through which a dry powder formulation is delivered to the lungs by patient’s inspiration. Characteristics such long shelf-life, portability and high delivery efficiency turns DPIs advantageous, comparatively to other existing types. Even though, a combination between device performance and powder engineering is needed for a successful delivery of drug particles in the desired region of the lung.
Aim: The aim of this study was to determine how different inhalation devices can influence the aerodynamic behavior of a formulation in specific parameters, such as: Emitted fraction (EF), Respirable fraction (RF) and Emitted respirable fraction (ERF).
Methods
Aerodynamic assessment of Fine Particle Fraction - Twin Stage Liquid Impinger (TSLI)
For each assay, five capsules (n=3) with the amount of complex correspondent to 1 mg of corticosteroid were prepared with 40mg of carrier (monohydrated lactose).
Two different devices were used: Rotahaler® (Glaxo Smith Kline) and Ingelheim Inhaler® (Boehringer Ingelheim).
TSLI was performed (4 compartments: device+capsules; mouth+throat; medium compartment; lower compartment - “Lungs”) at a flow rate of 60±5L/min during 15 seconds (5s×3). The corticosteroid measurable output in each compartment was quantified by HPLC analysis. Therefore it was possible to calculate the EF, the RF and the ERF.
Formulation strategy
Two formulations, A and B, were prepared by magnetic stirring of a hydroalcoholic solution of CyD and corticosteroid. Formulation A was prepared in a 2:1 CyD:Corticosteroid ratio and formulation B in a 3:1 ratio. The CyD and corticosteroid chosen were the same for both formulations.
Spray-drying was chosen among different formulation methods because it provided particles with better aerodynamic properties, which is essential for pulmonary delivery.
Results and Discussion
Table 1 summarizes the results obtained with both inhaler devices used: it can be seen that the Ingelheim Inhaler® provided an increased powder emission for both formulation A (+16.2%) and B (+18.3%) when compared to the Rotahaler’s results. The latter were relatively low (EF A and B< 75%) against the EF results for Ingelheim device that almost reached the 100% (EF A and B> 90%).
Table 1: TSLI results: EF, RF and ERF for the two devices used.
The same increase was noticed for the ERF results (Fig. 1). The Ingelheim Inhaler® was responsible for an increase of 12.6% (formulation A) and 6.5% (formulation B) in the ERF comparing to Rotahaler® device results. Figure 1 shows also that the ERF results obtained by the two devices are statistically different.
Despite formulation B had a higher EF increase (comparing to A), the resulting ERF increase was almost half than the registered for formulation A (12.6% vs. 6.5%). In general the two formulations presented excellent aerodynamic properties (40% of the emitted dose reach the lungs) and showed to be similar options for pulmonary delivery.
Figure 1. Comparison between ERF of the two different devices.
Conclusions
According to EF, RF and ERF of the two selected formulations it can be concluded that the Ingelheim Inhaler® device is more adequate to these formulations than the Rotahaler® device.
For the formulation A it was registered an EF increase of 16.2% (Rotahaler® vs. Ingelheim Inhaler®) that led to an ERF increase of 12.6% (78% of the EF increase reached the “Lungs”). So it can be concluded that the device is probably the main limiting factor for better aerodynamic performance for formulation A.
Concerning the formulation B an EF increase of 18.3% was observed (Rotahaler® vs. Ingelheim Inhaler®) leading to a shorter ERF increase: 6.5% (only 36% of the EF increase reached the “Lungs”). For the last case it seems the device is a limiting factor for better aerodynamic performance but the main limiting factor is probably the formulation itself.
It can be concluded that the delivery of these formulations to the lower compartment (“Lungs”) is dependent on the interconnection between powder formulation issues and device performance.
Acknowledgements
This work (PTDC/SAU-FCF/098733/2008) was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal.
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