Optimized dose delivery of the peptide cyclosporine using hydrofluoroalkane‐based metered dose inhalers

Myrdal, Paul B.; Karlage, Kelly L.; Stein, Steve W.; Brown, Beth; Haynes, Alfred

doi:10.1002/jps.20025

Cited by 31 publications

(21 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another important feature of Figures 4a and b is the prediction of smaller droplet size for HFA134a propellant system compared with HFA227 propellant system, by both atomization model variants. This trend was previously observed in several studies such as Brambilla et al (1999), Stein and Myrdal (2004), and Myrdal et al (2004), who measured the residual droplet size issued from a pMDI. The trend is attributable to higher saturated vapor pressure of HFA134a compared with HFA227, providing greater energy source for flow acceleration.…”

Section: Resultssupporting

confidence: 80%

Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

Gavtash

Versteeg

Hargrave

et al. 2017

Aerosol Science and Technology

View full text Add to dashboard Cite

Pressurized metered dose inhalers (pMDI) produce large numbers of droplets with smaller sizes than 5 mm to treat asthma and other pulmonary diseases. The mechanism responsible for droplet generation from bulk propellant liquid is poorly understood, mainly because the small length scales and short time scales make it difficult to characterize transient spray formation events. This article describes the development and findings of a numerical atomization model to predict droplet size of pharmaceutical propellants from first principles. In this model, the velocity difference between propellant vapor and liquid phase inside spray orifice leads to formation of wave-like instabilities on the liquid surface. Two variants of the aerodynamic atomization model are presented based on assumed liquid precursor geometry: (1) cylindrical jet-shaped liquid ligaments surrounded by vapor annulus; (2) annular liquid film with vapor flow in the core. The growth of instabilities on the liquid precursor surfaces and the size of the subsequently formed droplets are predicted by numerical solutions of dispersion equations. The droplet size predictions were compared with phase doppler anemometry (PDA) data and the predictions were in good agreement with the number mean diameter D 10 , which is representative of the respirable droplets. The temporal behavior of droplet size production was captured consistently well during the period of the first 95% of the propellant mass emission. The outcome of our modeling activities also suggests that, in addition to saturated vapor pressure of the propellant, its viscosity and surface tension are also key properties that govern pMDI droplet size. EDITORWarren Finlay

show abstract

Section: Resultssupporting

confidence: 80%

Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

Gavtash

Versteeg

Hargrave

et al. 2017

Aerosol Science and Technology

View full text Add to dashboard Cite

show abstract

“…This is about the minimum amount required (5 mg) to improve the pulmonary function of lung transplant patients with chronic rejection (Corcoran et al, 2004). This amount could be achieved with two capsules or a higher loading in a single capsule, compared with a metered dose inhaler formulation requiring five actuations to achieve approximately half the minimum amount required (Myrdal et al, 2004).…”

Section: Aerosol Performancementioning

confidence: 98%

“…Cyclosporine A (CsA) is an immunosuppressive agent used for the prevention of lung transplant rejections (Iacono et al, 2006), autoimmune disorders (Galeazzia, Bellisaia, Manganellia, Morozzia, & Sebastianib, 2006), and for the treatment of asthma (Underwood et al, 2001). CsA is soluble in hydrofluoroalkane propellants and used in pressured metered dose inhalers (pMDI) (Myrdal, Karlage, Stein, Brown, & Haynes, 2004). It has been shown by others that non-aqueous solutions of CsA could be spray dried to produce a liquid crystal form of CsA with mass median diameters of approximately 1.2 m, depending on the organic solvent and temperature used (Lechuga-Ballesteros et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A novel production method for inhalable cyclosporine A powders by confined liquid impinging jet precipitation

Chiou

Chan

Heng

et al. 2008

Journal of Aerosol Science

View full text Add to dashboard Cite

“…The instillation of liquids into pulmonary airways occurs in certain medical treatments such as surfactant replacement therapy (SRT) (Long et al 1991;Yapicioglu et al 2003;Salvia-Roiges et al 2004;Donn & Dalton 2009;Jeng, Soong & Lee 2009), partial liquid ventilation (Hirschl et al 2002;Cox et al 2003;Mikawa et al 2004;Guo et al 2009;Rasche et al 2010) and drug delivery (Jensen, Halpern & Grotberg 1994;Yu & Chien 1997;Zhang, Matar & Craster 2003;Iqbal et al 2004;Myrdal et al 2004). The effectiveness of these treatments depends on the ability to deliver the liquid into targeted areas.…”

Section: Introductionmentioning

confidence: 98%

Splitting of a two-dimensional liquid plug at an airway bifurcation

Vaughan

Grotberg

2016

J. Fluid Mech.

View full text Add to dashboard Cite

Certain medical treatments involve the introduction of exogenous liquids in the lungs. These liquids can form plugs within the airways. The plugs propagate throughout the branching network in the lungs being forced by airflow. They leave a deposited film on the airway walls and split at bifurcations. Understanding the resulting distribution of liquid throughout the lungs is important for the effective administration of the prescribed treatments. In this paper, we investigate numerically the splitting of a liquid plug by a two-dimensional pulmonary bifurcation under the influence of a transverse gravitational field. The splitting is characterized by the splitting ratio, which is the ratio of volume of the liquid plug in the daughter channels and depends on the capillary number and the orientation of the bifurcation plane with respect to a three-dimensional gravitational field. It is observed that gravity induces asymmetry in the splitting, causing the splitting ratio to be reduced. This effect is mitigated as the capillary number is increased. It is also observed that there exists a critical capillary number where the plug will not split and will instead propagate entirely into the gravitationally favoured daughter channel. We also compute the wall stresses on the bifurcation walls and observe the locations where stresses and their gradients are the highest in magnitude.

show abstract

Optimized dose delivery of the peptide cyclosporine using hydrofluoroalkane‐based metered dose inhalers

Cited by 31 publications

References 21 publications

Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)

A novel production method for inhalable cyclosporine A powders by confined liquid impinging jet precipitation

Splitting of a two-dimensional liquid plug at an airway bifurcation

Contact Info

Product

Resources

About