title: Development of a new technique for the efficient delivery of aerosolized medications to infants on mechanical ventilation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA, pwlongest@vcu.edu.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
mesh_terms: D000336:Aerosols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007223:Infant; D001239:Inhalation / Q000502:physiology; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism; D008297:Male; D010316:Particle Size; D012121:Respiration, Artificial; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D005079:Excipients
references.citation: Respir Care. 2004 Jun;49(6):653-65
references.pmid: 15165300
references.citation: J Biomech Eng. 2013 Sep;135(9):91010
references.pmid: 23722698
references.citation: Pharm Res. 2013 Jun;30(6):1608-27
references.pmid: 23471640
references.citation: Pediatr Pulmonol. 1996 May;21(5):301-9
references.pmid: 8726155
references.citation: Pharm Res. 2013 Nov;30(11):2917-30
references.pmid: 23801087
references.citation: Pediatr Crit Care Med. 2013 Feb;14(2):e98-102
references.pmid: 23287904
references.citation: Thorax. 1996 Jan;51(1):75-7
references.pmid: 8658374
references.citation: Eur J Pharm Sci. 2013 Jun 14;49(3):390-9
references.pmid: 23608613
references.citation: J Aerosol Med Pulm Drug Deliv. 2013 Oct;26(5):266-79
references.pmid: 23273243
references.citation: J Aerosol Sci. 2010 Aug 1;41(8):805-820
references.pmid: 20835406
references.citation: Respir Care. 2014 May;59(5):686-98
references.pmid: 24106320
references.citation: Anat Rec. 1985 Aug;212(4):368-80
references.pmid: 4073554
references.citation: Pediatr Res. 2005 Jul;58(1):10-4
references.pmid: 15774850
references.citation: Aerosol Sci Technol. 2011 Jan 1;45(7):884-899
references.pmid: 21804683
references.citation: Pediatr Res. 1997 Nov;42(5):721-7
references.pmid: 9357949
references.citation: Respir Care Clin N Am. 2001 Jun;7(2):175-213, v
references.pmid: 11517020
references.citation: Adv Drug Deliv Rev. 2012 Mar 30;64(4):296-311
references.pmid: 21640772
references.citation: J Aerosol Med. 2006 Winter;19(4):473-83
references.pmid: 17196076
references.citation: J Aerosol Med Pulm Drug Deliv. 2014 Oct;27(5):371-85
references.pmid: 24299500
references.citation: Eur J Pediatr. 2011 Apr;170(4):433-44
references.pmid: 20878336
references.citation: J Aerosol Med Pulm Drug Deliv. 2013 Oct;26(5):248-65
references.pmid: 23286828
references.citation: Pharm Res. 2012 Jun;29(6):1670-88
references.pmid: 22290350
references.citation: Ann Biomed Eng. 2012 Dec;40(12):2596-610
references.pmid: 22820981
references.citation: Ann Biomed Eng. 2013 Jun;41(6):1217-32
references.pmid: 23423706
references.citation: Respir Care. 2010 Jul;55(7):845-51
references.pmid: 20587095
references.citation: J Appl Physiol (1985). 2003 Nov;95(5):2106-12
references.pmid: 12897033
references.citation: J Aerosol Sci. 2012 Sep;51:66-80
references.pmid: 22707794
references.citation: J Biomech. 2007;40(2):305-16
references.pmid: 16533511
references.citation: J Appl Physiol (1985). 2008 Jun;104(6):1761-77
references.pmid: 18388247
references.citation: Int J Pharm. 2013 Feb 25;443(1-2):137-45
references.pmid: 23313343
references.citation: Pharm Res. 2014 Feb;31(2):360-72
references.pmid: 23949304
references.citation: Curr Opin Crit Care. 2007 Feb;13(1):27-38
references.pmid: 17198046
references.citation: Respir Care. 2011 Sep;56(9):1411-21; discussion 1421-3
references.pmid: 21944688
references.citation: Pharm Res. 2012 Mar;29(3):707-21
references.pmid: 21948458
references.citation: J Pharm Pharmacol. 2012 Sep;64(9):1254-63
references.pmid: 22881438
references.citation: J Aerosol Med Pulm Drug Deliv. 2013 Dec;26(6):370-9
references.pmid: 23421901
references.citation: J Aerosol Med Pulm Drug Deliv. 2014 Feb;27(1):58-65
references.pmid: 23509937