Modulite®: a means of designing the aerosols generated by pressurized metered dose inhalers

Ganderton, D.; Lewis, David; Davies, Robert J.; Meakin, B. J.; Brambilla, G.; Church, Tanya

doi:10.1016/s0954-6111(02)80018-x

Cited by 59 publications

(40 citation statements)

References 3 publications

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“…Unfortunately, despite the widespread availability of these combination therapies, many patients with asthma remain poorly controlled [9]. A fixed ICS/LABA combination pressurized metered dose inhaler (pMDI) containing extrafine beclometasone dipropionate (BDP 100 mg) and formoterol fumarate (6 mg) (Foster®, Chiesi Farmaceutici, Italy) has been recently developed using proprietary Modulite® (Chiesi Farmaceutici, Italy) technology [10]. This technology allows the drug particle size to be tailored, thus enabling the development of extra-fine formulations with an improved lung deposition [11].…”

Section: Introductionmentioning

confidence: 99%

Effect of AeroChamber Plus™ on the lung and systemic bioavailability of beclometasone dipropionate/formoterol pMDI

Singh

Collarini²,

Poli³

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Use of a spacer minimizes oropharyngeal deposition and optimizes drug targeting to the airways in subjects with coordination difficulties. However, the increase in pulmonary deposition often observed with spacer devices, could potentially lead to an increase in overall systemic exposure.• EMA guidelines recommend that the development of a pMDI should always include testing of at least one specific spacer for use with a particular pMDI.• The aim of this study was to examine the effect of AeroChamber Plus™ on the lung bioavailability and total systemic exposure of a hydrofluoroalkane (HFA) pMDI fixed combination of extra‐fine beclometasone dipropionate/formoterol (100/6 µg) (Foster®).WHAT THIS STUDY ADDS• The use of AeroChamber Plus™ optimizes the lung delivery of beclometasone and formoterol in subjects that find it difficult to synchronize aerosol actuation with the inspiration of breath.• The total systemic exposure of beclometasone 17‐monopropionate and formoterol was not significantly increased by the use of the AeroChamber Plus™ spacer.• Use of the AeroChamber Plus™ spacer device with the extra‐fine beclometasone dipropionate/formoterol (100/6 µg) fixed combination pMDI can be a valuable option for certain patients groups, such as subjects with difficulties in achieving an adequate inhalation technique.AIM To assess the effect of AeroChamber Plus™ on lung deposition and systemic exposure to extra‐fine beclometasone dipropionate (BDP)/formoterol (100/6 µg) pMDI (Foster®). The lung deposition of the components of the combination given with the pMDI was also evaluated using the charcoal block technique.METHODS Twelve healthy male volunteers received four inhalations of extra‐fine BDP/formoterol (100/6 µg) using (i) pMDI alone, (ii) pMDI and AeroChamber Plus™ and (iii) pMDI and charcoal ingestion.RESULTS Compared with pMDI alone, use of AeroChamber Plus™ increased the peak plasma concentrations (Cmax) of BDP (2822.3 ± 1449.9 vs. 5454.9 ± 3197.1 pg ml−1), its active metabolite beclometasone 17‐monopropionate (17‐BMP) (771.6 ± 288.7 vs. 1138.9 ± 495.6 pg ml−1) and formoterol (38.4 ± 17.8 vs. 54.7 ± 20.0 pg ml−1). For 17‐BMP and formoterol, the AUC(0,30 min), indicative of lung deposition, was increased in the AeroChamber Plus™ group by 41% and 45%, respectively. This increase was mainly observed in subjects with inadequate inhalation technique. However, use of AeroChamber Plus™ did not increase the total systemic exposure to 17‐BMP and formoterol. Results after ingestion of charcoal confirmed that AUC(0,30 min) can be taken as an index of lung bioavailability and that more than 30% of the inhaled dose of extra‐fine BDP/formoterol 100/6 µg was delivered to the lung using the pMDI alone.CONCLUSIONS The use of AeroChamber Plus™ optimizes the delivery of BDP and formoterol to the lung in subjects with inadequate inhalation technique. The total systemic exposure was not increased, supporting the safety of extra‐fine BDP/formoterol pMDI with AeroChamber Plus™.

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Section: Introductionmentioning

confidence: 99%

Effect of AeroChamber Plus™ on the lung and systemic bioavailability of beclometasone dipropionate/formoterol pMDI

Singh

Collarini²,

Poli³

et al. 2011

Brit J Clinical Pharma

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“…Drug permeability studies were conducted on cell layers between 12 and 14 days after seeding. This period was previously determined as optimal by Haghi et al [6,16].…”

Section: Cell Culturementioning

confidence: 99%

“…For example, BDP was formulated as an ultrafine inhalation aerosol by solubilising the drug in an ethanol-HFA 134a-based system [5]. Similarly, Modulite™ technology utilised an ethanol-HFA-based solution, but additionally incorporated non-volatile components, such as glycerol, to generate a larger mass median aerodynamic diameter (MMAD), equivalent to that of the original CFC-based systems [6]. While the former approach required extensive clinical trials due to different regional lung deposition [7], the Modulite technology was tuned to have a similar deposition profiles to that of the former CFC formulations.…”

Section: Introductionmentioning

confidence: 99%

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Haghi

Bebawy

Colombo

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tTwo solution-based pressurised metered dose inhaler (pMDI) formulations were prepared such that they delivered aerosols with identical mass median aerodynamic diameters, but contained either beclomethasone dipropionate (BDP) alone (glycerol-free formulation) or BDP and glycerol in a 1:1 mass ratio (glycerol-containing formulation). The two formulations were deposited onto Calu-3 respiratory epithelial cell layers cultured at an air interface. Equivalent drug mass ($1000 ng or $2000 ng of the formulation) or equivalent particle number (1000 ng of BDP in the glycerol-containing versus 2000 ng of BDP in the glycerol-free formulation) were deposited as aerosolised particles on the air interfaced surface of the cell layers. The transfer rate of BDP across the cell layer after deposition of the glycerol-free particles was proportional to the mass deposited. In comparison, the transfer of BDP from the glycerol-containing formulation was independent of the mass deposited, suggesting that the release of BDP is modified in the presence of glycerol. The rate of BDP transfer (and the extent of metabolism) over 2 h was faster when delivered in glycerol-free particles, 465.01 ng ± 95.12 ng of the total drug (20.99 ± 4.29%; BDP plus active metabolite) transported across the cell layer, compared to 116.17 ng ± 3.07 ng (6.07 ± 0.16%) when the equivalent mass of BDP was deposited in glycerol-containing particles. These observations suggest that the presence of glycerol in the maturated aerosol particles may influence the disposition of BDP in the lungs.

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“…24 These new generations of pMDIs use hydrofluoroalkane (HFA) propellants. While some of the HFA devices were matched to their CFC counterparts on a dose-for-dose basis, 25 the switch to HFA inhalers also offered the opportunity to completely redesign the pMDI. New formulations of pMDIs can dispense aerosols with smaller particle sizes and lower plume velocities.…”

Section: Inhaler Devices For Asthma Therapy Pressurised Metered Dose mentioning

confidence: 99%

Inhaler Characteristics in Asthma

Biddiscombe¹

2017

European Respiratory &Amp; Pulmonary Diseases

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The history of inhaled therapy goes back a surprisingly long way. More than 4,000 years ago, in India, the vapour of plants from the nightshade family placed on hot bricks was inhaled to alleviate breathing difficulties. The bronchodilators, derived from these plants, and compounds related to them, have played a significant part in therapeutic aerosol delivery over the years and remain important in the treatment of lung diseases today. The development of inhaled therapy has accelerated over the past 60 years with the arrival of the first truly portable inhaler in 1956 to relieve the symptoms of asthma. Initially, only bronchodilators were delivered from these devices, but as the true nature of asthma was revealed, inhaled corticosteroids were introduced to treat the underlying inflammation that is a major component of asthma. Further advances have led to long-acting bronchodilators becoming available, and combination therapies containing both longacting bronchodilators and corticosteroids in one inhaler. Asthma therapy has come a long way in a comparatively short time with over 230 device and drug combinations available for treating the disease. However, despite enormous investment asthma remains a huge healthcare problem. The number of people with asthma continues to grow with over 300 million people affected worldwide and 250,000 annual deaths attributed to the disease. It affects people of all ages and has a varying degree of severity. In this article, we look at the ideal characteristics for asthma inhalers and highlight some of the most important reasons for the failure of current asthma treatments.

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Modulite®: a means of designing the aerosols generated by pressurized metered dose inhalers

Cited by 59 publications

References 3 publications

Effect of AeroChamber Plus™ on the lung and systemic bioavailability of beclometasone dipropionate/formoterol pMDI

Effect of AeroChamber Plus™ on the lung and systemic bioavailability of beclometasone dipropionate/formoterol pMDI

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Inhaler Characteristics in Asthma

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