Inhalable tranexamic acid for haemoptysis treatment.
OBJECTIVE
An inhalable dry powder formulation of tranexamic acid (TA) was developed and tested in a novel high-dose Orbital® multi-breath inhaler. The formulation was specifically intended for the treatment of pulmonary haemorrhage and wound healing associated with haemoptysis.


METHODS
Inhalable TA particles were prepared by spray drying and the powder characterised using laser diffraction, electron microscopy, thermal analysis, moisture sorption and X-ray powder diffraction. The aerosol performance was evaluated using cascade impaction and inline laser diffraction and interaction with epithelia cells and wound healing capacity investigated using Calu-3 air interface model.


RESULTS
The spray dried TA particles were crystalline and spherical with a D0.5 of 3.35 μm. The powders were stable and had limited moisture sorption (0.307%w/w at 90%RH). The Orbital device delivered ca. 38 mg powder per 'inhalation' at 60 l · min(-1) across four sequential shots with an overall fine particle fraction (⩽ 6.4 μm) of 59.3 ± 3.5% based on the emitted mass of ca. 150 mg. The TA particles were well tolerated by Calu-3 bronchial epithelia cells across a wide range of doses (from 1 nM to 10nM) and no increase in inflammatory mediators was observed after deposition of the particles (a decrease in IL-1β, IL-8 and INFγ was observed). Time lapse microscopy of a damaged confluent epithelia indicated that wound closure was significantly greater in TA treated cells compared to control.


CONCLUSIONS
A stable, high performance aerosol of TA has been developed in a multi-breath DPI device that can be used for the treatment of pulmonary lesions and haemoptysis.
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia.
Mehra
M
Haghi
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia; Avans University of Applied Sciences, Hogeschoollaan 1, 4818 CR Breda, The Netherlands.
Wilco
W
van den Oetelaar
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia.
Lyn M
LM
Moir
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia.
Bing
B
Zhu
Pharmaxis Ltd, 20 Rodborough Rd, Frenchs Forest, NSW 2086, Australia.
Gary
G
Phillips
Pharmaxis Ltd, 20 Rodborough Rd, Frenchs Forest, NSW 2086, Australia.
John
J
Crapper
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia.
Paul M
PM
Young
Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia. Electronic address: Daniela.traini@sydney.edu.au.
Daniela
D
Traini
D000280:Administration, Inhalation; D000336:Aerosols; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004867:Equipment Design; D006469:Hemoptysis / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D018715:Microscopy, Video; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D013997:Time Factors; D059008:Time-Lapse Imaging; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
D000336:Aerosols; D000933:Antifibrinolytic Agents; D018836:Inflammation Mediators; D011208:Powders; D014148:Tranexamic Acid
Calu-3; Haemoptysis; Orbital multi breath inhaler; Tranexamic acid; Wound healing