A Novel Continuous Powder Aerosolizer (CPA) for Inhalative Administration of Highly Concentrated Recombinant Surfactant Protein-C (rSP-C) Surfactant to Preterm Neonates

Pöhlmann, G.; Iwatschenko, P; Koch, Wolfgang; Windt, H.; Rast, Markus; Abreu, M. Gama de; Taut, Friedemann; Muynck, C. De

doi:10.1089/jamp.2012.0996

Cited by 40 publications

(35 citation statements)

References 19 publications

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“…As reviewed by Harper et al (2007), the Exubera ® device uses a compressed air source and a well designed flow channel. Similarly, the continuous powder aerosolizer of Pohlmann et al (2013) implements repeated pulses of air for producing the aerosol. Ultrasound and other vibration inducing techniques are also available for active deaggregation (Corcoran et al, 2013; Crowder and Hickey, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Relatively few studies have considered the use of active DPIs for aerosol delivery compared with passive devices (Everard et al, 1996; Grainger et al, 2004; Harper et al, 2007; Pohlmann et al, 2013; Tang et al, 2011; Ungaro et al, 2006). Considering the use of active devices with mechanical ventilation systems, Everard et al (1996) aerosolized budesonide through straight endotracheal tubes (9.0 mm internal diameter and 32 cm in length) using the Turbuhaler ® DPI enclosed in an airtight casing, and reported 20% mean drug delivery through the system at an inspiratory tracheal flow rate of approximately 60 LPM.…”

Section: Introductionmentioning

confidence: 99%

“…The authors reported 90% emitted dose from the Solovent device with a majority of the powder retained in the spacer, resulting in a range of approximately 0.3–4% deposition on a filter positioned distal to the SAINT model. Pohlmann et al (2013) recently demonstrated the continuous delivery of high dose spray dried surfactants to infants and neonates receiving mechanical ventilation using an active DPI system and reported a delivery efficiency of 55% prior to the patient interface, which was envisioned to be infant nasal prongs. Based on these studies and others, active DPI devices used during mechanical ventilation or with a mask typically deliver approximately 0.3–60% of the aerosolized drug to the lungs and provide FPFs < 5 μm of approximately 20–30%.…”

Section: Introductionmentioning

confidence: 99%

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Development of high efficiency ventilation bag actuated dry powder inhalers

Behara

Longest

Farkas

et al. 2014

International Journal of Pharmaceutics

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New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70–80% with fine particle fractions <5 μm of 65–85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3 mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15 LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of high efficiency ventilation bag actuated dry powder inhalers

Behara

Longest

Farkas

et al. 2014

International Journal of Pharmaceutics

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“…The equivocal results with various first generation liquid surfactant preparations have hampered progress in this field, but the development of new liquid and dry powder nebulizers and advances in synthetic surfactant design will surely provide new impetus. Several research groups have explored the potential of dry powder aerosolization of a recombinant SP-C surfactant (Venticute ® , Nycomed GmbH, Konstanz, Germany) in mice, rabbits and premature lambs and shown its potential to deliver high doses comparable to those used for intratracheal bolus instillation (Ruppert et al, 2010; Rahmel et al, 2012; Pohlmann et al, 2013). However, surface activity of the recombinant SP-C surfactant has recently come under attack after disappointing results in clinical studies of patients with acute lung injury (Spragg et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Aerosol delivery of synthetic lung surfactant

Walther

Hernández-Juviel

Waring

2014

PeerJ

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Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant.Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits.Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant), with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity), we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV.Results. Particle size distribution of the surfactant aerosols was within the 1–3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of ventilatory support (nCPAP or MV) used.Conclusions. Aerosol delivery of synthetic lung surfactant with a combination of highly active second generation SP-B and SP-C mimics was effective as a therapeutic approach towards relieving surfactant deficiency in spontaneously breathing rabbits supported with nCPAP. To obtain similar results with nCPAP as with intratracheal instillation, higher dosage of synthetic surfactant and reduction of its retention by the delivery circuit will be needed to increase the lung dose.

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“…Based on an in vitro model of ventilated premature infants, Mazela et al (14) reported delivery efficiency at the exit of a commercial Y-connector to be approximately 1% or less vs. a maximum of approximately 7% with the VC connector. Pohlmann et al (15) developed an aerosol device for delivering high concentrations of a spray dried surfactant formulation to infants through a nasal cannula interface. The powder was aerosolized using a new pulsed air device, coated with water in a separate chamber, and then delivered to the patient interface.…”

Section: Introductionmentioning

confidence: 99%

Development of a New Technique for the Efficient Delivery of Aerosolized Medications to Infants on Mechanical Ventilation

Longest

Tian

2014

Pharm Res

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Purpose To evaluate the efficiency of a new technique for delivering aerosols to intubated infants that employs a new Y-connector, access port administration of a dry powder, and excipient enhanced growth (EEG) formulation particles that change size in the airways. Methods A previously developed CFD model combined with algebraic correlations were used to predict delivery system and lung deposition of typical nebulized droplets (MMAD = 4.9 μm) and EEG dry powder aerosols. The delivery system consisted of a Y-connector [commercial (CM); streamlined (SL); or streamlined with access port (SL-port)] attached to a 4-mm diameter endotracheal tube leading to the airways of a 6-month-old infant. Results Compared to the CM device and nebulized aerosol, the EEG approach with an initial 0.9 μm aerosol combined with the SL and SL-port geometries reduced device depositional losses by factors of 3-fold and >10-fold, respectively. With EEG powder aerosols, the SL geometry provided the maximum tracheobronchial deposition fraction (55.7%), whereas the SL-port geometry provided the maximum alveolar (67.6%) and total lung (95.7%) deposition fractions, respectively. Conclusions Provided the aerosol can be administered in the first portion of the inspiration cycle, the proposed new method can significantly improve the deposition of pharmaceutical aerosols in the lungs of intubated infants.

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A Novel Continuous Powder Aerosolizer (CPA) for Inhalative Administration of Highly Concentrated Recombinant Surfactant Protein-C (rSP-C) Surfactant to Preterm Neonates

Cited by 40 publications

References 19 publications

Development of high efficiency ventilation bag actuated dry powder inhalers

Development of high efficiency ventilation bag actuated dry powder inhalers

Aerosol delivery of synthetic lung surfactant

Development of a New Technique for the Efficient Delivery of Aerosolized Medications to Infants on Mechanical Ventilation

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