Modulite® technology: pharmacodynamic and pharmacokinetic implications

Woodcock, Ashley; Acerbi, Daniela; Poli, Gianluigi

doi:10.1016/s0954-6111(02)80019-1

Cited by 40 publications

(24 citation statements)

References 11 publications

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“…The MMAD of the glycerol-free and glycerol-containing formulations, measured via ACI stage deposition data, was 2.4 ± 0.1 lm and 2.5 ± 0.2 lm, respectively (n = 3). No significant difference in stage-by-stage deposition or fine particle fraction/ mass was observed between the two formulations used [8,15]. It is important to note, however, that for the mass of drug emitted by both formulations to be similar, the number of particles (and formulation mass, including excipient) would be different.…”

Section: Resultsmentioning

confidence: 99%

“…4 lm) [3]. The area under the plasma concentration curve for the BMP in the Modulite formulations was reported to be markedly different than QVAR, but not dissimilar to the CFC formulations even though the MMAD's were different [8]. In addition, the Modulite formulations were shown to have similar clinical outcomes to CFC formulations in terms of Forced Expiratory Volume and morning serum cortisol concentrations [9].…”

Section: Introductionmentioning

confidence: 96%

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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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“…Moreover, the jet orifice diameter was increased, making the spray plume similar to that of CFC. 30,31 Nowadays, BDP-Modulite ® and budesonideModulite ® are available in the international market The advantage of Modulite ® technology is that it bears a striking resemblance to the pMDI that use CFC propellant. This allows the CFC/HFA transition to be more easily planned, since it is not necessary to change the doses used, as pulmonary deposition and absorption are similar to those of CFC-containing pMDI because the particle size is similar.…”

Section: -23mentioning

confidence: 99%

Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança

Ibiapina¹,

Cruz²,

Camargos³

2004

J. Pediatr. (Rio J.)

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Objective: To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs.Sources of data: Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS) and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out.Summary of the findings: 43 original articles on the replacement of clorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < 0.003) in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers.Conclusions: Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced, as well as, in general, there was a better pulmonary deposition of particles. However, literature data on the use of hydrofluoralkane in the paediatric age group are still scarce and further studies with children and adolescents would be of great importance.

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“…There is some evidence to suggest that the targeting of drug deposition from pMDIs containing HFA propellants is not significantly influenced by the addition of a spacer. [11][12][13] In addition, selection of spacer design may also be unimportant for drug delivery to the periphery of the lung. 8,14 Dubus et al showed salbutamol (albuterol) responses were not significantly different between spacer devices when an HFA134a formulation was used.…”

Section: Introductionmentioning

confidence: 99%

“…11 It has also been shown that use of a spacer with or without an HFA formulation did not change the plasma profiles of beclomethasone dipropionate. 12 Hirst et al showed lung deposition of triamcinolone acetonide by mass was similar with (188 µg) or without spacer (175 µg) setup. 13 Williams et al analyzed a wide range of spacer devices across a solution HFA system (beclomethasone valerate) and a suspension system (triamcinolone acetonide).…”

Section: Introductionmentioning

confidence: 99%

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

Smyth¹,

Beck²,

Williams³

et al. 2004

AAPS PharmSciTech

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INTRODUCTIONThe purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2,-tetrafluoroethane] propellant. Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber, and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI). Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at ~0.5 µm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately 0 when spacer devices were used with either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (~25% of emitted dose compared with 69%, respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance. This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly lowered sampling inlet deposition when no spacer was used.Pressurized metered dose inhalers (pMDIs) have proved an effective means of administering drugs to respiratory tract in the treatment and management of asthma. 1 However, reproducibility of dosing has been a concern with these devices because of noncompliance in prescribed usage. 2 Accurate dosing is especially necessary in cases where immediate pharmacodynamic feedback is not useful for dosage regulation, as in the case for corticosteroids employed for longterm maintenance therapy for asthma. Dose-related systemic side effects occur secondary to absorption of drug from mouth, throat, gastrointestinal tract, and lungs. Variability in dosing may result in too much or, more significantly, too little drug being delivered, with consequences for disease management. Noncompliant use of pMDIs is associated with the difficulty of inhalation-actuation coordination (particularly for children and elderly users). 3 As a consequence, devices such as spacers have been developed for use with pMDIs to improve dosing reproducibility and reduce unwanted oral deposition of aerosol droplets. 4 Spacers function by reducing the aerosol velocity, allowing time for evaporation and sedimentation, thus reducing deposition of large particles in the mouth and throat. 4 Additionally, it has been shown that spacers increase the fine particle dose (FPD) t...

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Modulite® technology: pharmacodynamic and pharmacokinetic implications

Cited by 40 publications

References 11 publications

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

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

Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

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