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Comparison Of Bioavailability Of Amorphous Versus Crystalline Itraconazole Nanoparticles Via Pulmonary Administration In Rats.

W. Yang, K. Johnston, R. Williams
Published 2010 · Chemistry, Medicine

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The effect of supersaturation on bioavailability of inhaled nebulized aerosols is compared for amorphous versus crystalline nanoparticulate dispersions. The nanocrystalline formulations of itraconazole (ITZ) were made by wet milling (i.e. Wet-milled ITZ), whereas amorphous nanostructured aggregates (ITZ/mannitol/lecithin=1:0.5:0.2, weight ratio) were made by an ultra-rapid freezing process (i.e. URF-ITZ). Dissolution tests revealed the extent of supersaturation was 4.7-times higher for URF-ITZ versus Wet-milled ITZ, though their dissolution rates were similar. The aerodynamic performances of both aqueous colloidal dispersions were comparable and suitable for deep lung delivery. Single-dose 24-h pharmacokinetic studies were conducted in Sprague-Dawley rats following inhalation of the nebulized colloidal dispersions (equivalent to 20mgITZ/mL dispersion in 5mL) in a nose-only dosing apparatus. Lung depositions following inhalation were similar for both compositions. In systemic circulation, Wet-milled ITZ and URF-ITZ achieved C(max) of 50 and 180ng/mL at 2.7 and 4.0h, and AUC(0-24) of 662 and 2543ngh/mL, respectively, based on a one-compartmental analysis. Pulmonary delivery of the nanoparticulate amorphous ITZ composition resulted in significantly higher systemic bioavailability than for the nanocrystalline ITZ composition, as a result of the higher supersaturation that increased the permeation.
This paper references
10.1016/j.ijpharm.2008.11.029
Development of an oral rutin nanocrystal formulation.
R. Mauludin (2009)
10.1038/nrd2153
Inhaling medicines: delivering drugs to the body through the lungs
John S. Patton (2007)
10.1016/J.IJPHARM.2007.10.001
Understanding a relaxation behavior in a nanoparticle suspension for drug delivery applications.
Z. Deng (2008)
10.1016/0378-5173(89)90069-0
The effect of particle size distribution on dissolution rate and oral absorption
R. J. Hintz (1989)
10.1021/JS960075U
Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery.
R. Rajewski (1996)
10.1016/J.ADDR.2007.05.011
Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.
N. Blagden (2007)
10.1021/mp800106a
Highly supersaturated solutions from dissolution of amorphous itraconazole microparticles at pH 6.8.
Michal E. Matteucci (2009)
10.1016/J.JCONREL.2005.06.009
Microparticle-based lung delivery of INH decreases INH metabolism and targets alveolar macrophages.
H. Zhou (2005)
10.1021/MP0700211
Design of potent amorphous drug nanoparticles for rapid generation of highly supersaturated media.
Michal E. Matteucci (2007)
10.1007/s11671-008-9234-1
Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery
Po-Chang Chiang (2009)
10.1021/MP049938F
Physical stability and solubility advantage from amorphous celecoxib: the role of thermodynamic quantities and molecular mobility.
P. Gupta (2004)
10.1016/S1056-8719(00)00107-6
Drug-like properties and the causes of poor solubility and poor permeability.
C. Lipinski (2000)
10.1002/JPS.2600650533
Enhancement of solubility of drug salts by hydrophilic counterions: properties of organic salts of an antimalarial drug.
S. Agharkar (1976)
10.1016/j.ijpharm.2008.09.022
Formulation and pharmacokinetic evaluation of an asulacrine nanocrystalline suspension for intravenous delivery.
Srinivas Ganta (2009)
10.1615/CRITREVTHERDRUGCARRIERSYST.V19.I45.40
Pulmonary drug delivery systems: recent developments and prospects.
H. Courrier (2002)
10.1164/AJRCCM.164.9.2101036
Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster.
A. Nemmar (2001)
10.1007/s11095-006-9174-3
Particle Engineering for Pulmonary Drug Delivery
Albert H. L. Chow (2006)
10.1016/S0928-0987(02)00057-X
Eudragit RS100 nanosuspensions for the ophthalmic controlled delivery of ibuprofen.
R. Pignatello (2002)
10.1002/JPS.2600560712
Effect of polymorphism on the absorption of chloramphenicol from chloramphenicol palmitate.
A. Aguiar (1967)
10.1016/J.JCONREL.2005.01.003
Novel sustained release microspheres for pulmonary drug delivery.
R. O. Cook (2005)
10.1016/s0169-409x(96)00423-1
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.
C. Lipinski (2001)
10.1093/TOXSCI/KFJ084
Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles.
P. Borm (2006)
10.1211/jpp.59.8.0002
Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in‐vitro characterization, ex‐vivo and in‐vivo studies
V. Sanna (2007)
10.1016/J.EJPB.2006.07.012
Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs.
Kirk A. Overhoff (2007)
10.1211/0022357023691
Nanosuspensions: a promising drug delivery strategy
V. Patravale (2004)
10.1201/9781315159768
Inhalation Aerosols : Physical and Biological Basis for Therapy, Third Edition
A. Hickey (2019)
10.1177/0091270003261490
The Pharmacokinetics of Nebulized Nanocrystal Budesonide Suspension in Healthy Volunteers
W. Kraft (2004)
10.1016/j.ijpharm.2008.05.003
High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers.
W. Yang (2008)
10.1016/j.ijpharm.2008.02.011
Inhaled nanoparticles--a current review.
W. Yang (2008)
10.1002/jps.21367
Amorphous cyclosporin nanodispersions for enhanced pulmonary deposition and dissolution.
J. Tam (2008)
10.1016/S0939-6411(00)00076-X
Improving drug solubility for oral delivery using solid dispersions.
C. Leuner (2000)
10.1007/s11095-006-9132-0
Micellar Nanocarriers: Pharmaceutical Perspectives
V. Torchilin (2006)
10.1016/J.JCONREL.2006.11.011
Turbidimetric measurement and prediction of dissolution rates of poorly soluble drug nanocrystals.
M. T. Crisp (2007)
10.1016/J.IJPHARM.2004.07.019
The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs.
J. Kipp (2004)
10.1023/A:1012024021511
Nebulization of NanoCrystals™: Production of a Respirable Solid-in-Liquid-in-Air Colloidal Dispersion
T. Wiedmann (2004)
10.1007/s11095-006-9904-6
Targeted High Lung Concentrations of Itraconazole Using Nebulized Dispersions in a Murine Model
J. McConville (2006)
10.1128/AAC.50.4.1552-1554.2006
In Vivo Efficacy of Aerosolized Nanostructured Itraconazole Formulations for Prevention of Invasive Pulmonary Aspergillosis
B. J. Hoeben (2006)
10.1002/JPS.10126
Characterization of the interaction of 2-hydroxypropyl-beta-cyclodextrin with itraconazole at pH 2, 4, and 7.
J. Peeters (2002)
10.1002/JPS.20806
Hot-melt extrusion for enhanced delivery of drug particles.
D. Miller (2007)
10.1016/J.IJPHARM.2007.03.011
Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs.
M. Kassem (2007)
10.3109/03009739009178581
Intrapulmonary deposition of aerosolized Evans blue dye and liposomes in an experimental porcine model of early ARDS.
P. Forsgren (1990)
10.1016/J.EJPB.2006.01.006
Single dose and multiple dose studies of itraconazole nanoparticles.
J. M. Vaughn (2006)
10.1016/S0168-3659(02)00370-X
Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features.
L. A. Dailey (2003)
10.1016/S0169-409X(00)00118-6
Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future.
R. Mueller (2001)
10.1016/0378-5173(95)00122-Y
Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs
G. Liversidge (1995)
10.1201/9781420026054
Water-insoluble drug formulation
R. Liu (2000)
10.1002/JPS.20135
Lyophilization of polyethylene glycol mixtures.
K. Amin (2004)
10.1016/J.JPBA.2005.05.014
A new approach in the prediction of the dissolution behavior of suspended particles by means of their particle size distribution.
A. Tinke (2005)
10.1023/A:1007516718048
What is the True Solubility Advantage for Amorphous Pharmaceuticals?
Bruno C. Hancock (2004)
10.1002/JPS.2600580817
Dissolution behavior of polymorphs of chloramphenicol palmitate and mefenamic acid.
A. Aguiar (1969)
10.1021/JS9601896
Characteristics and significance of the amorphous state in pharmaceutical systems.
Bruno C. Hancock (1997)
10.1016/j.ejpb.2008.01.037
Nebulization of nanoparticulate amorphous or crystalline tacrolimus--single-dose pharmacokinetics study in mice.
Prapasri Sinswat (2008)
10.1002/JPS.10489
Physics of amorphous solids.
L. R. Hilden (2004)
10.1016/0378-5173(95)04114-1
Enhancement of dissolution of glyburide by solid dispersion and lyophilization techniques
G. Betageri (1995)
10.1023/A:1018913311788
Deposition Patterns of Aerosolized Drugs Within Human Lungs: Effects of Ventilatory Parameters
T. Martonen (2004)
10.1021/jp805991f
Highly supersaturated solutions of amorphous drugs approaching predictions from configurational thermodynamic properties.
Michal E. Matteucci (2008)



This paper is referenced by
10.1016/j.ijpharm.2017.09.024
Development of fine solid-crystal suspension with enhanced solubility, stability, and aerosolization performance for dry powder inhalation.
L. Lin (2017)
Production of stable bcs class ii drug suspensions by melt emulsification and subsequent incorporation into polymer strip films
Emanuel Vizzotti (2013)
10.1016/j.ijpharm.2013.04.032
Coamorphous repaglinide-saccharin with enhanced dissolution.
Y. Gao (2013)
A stable hydrocortisone nanosuspension for improved dissolution: Preparation, characterization and in vitro evaluation.
Hany S M Ali (2017)
10.1016/J.CEJ.2011.12.044
Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: Recent developments and future perspective
Alpana Ankush Thorat (2012)
Original Research Paper A FACILE APPROACH TO ENHANCE SOLUBILITY AND DISSOLUTION RATE OF NORFLOXACIN BY NANOPLEX
Raosaheb S. Shendge (2014)
10.1016/j.ijpharm.2013.11.042
The impact of pulmonary diseases on the fate of inhaled medicines--a review.
Yi-bo Wang (2014)
10.1201/B19976-6
Nanotechnology for Pulmonary and Nasal Drug Delivery
Helene Dugas (2016)
10.2174/2211738504666160213001714
Polymer-drug nanoconjugate – an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs.
A. Abioye (2016)
10.4155/tde.15.21
Understanding pharmaceutical polymorphic transformations II: crystallization variables and influence on dosage forms.
J. Sood (2015)
10.1016/j.ejpb.2017.08.012
Enhanced transmucosal delivery of itraconazole by thiolated d‐&agr;‐tocopheryl poly(ethylene glycol) 1000 succinate micelles for the treatment of Candida albicans
J. Suksiriworapong (2017)
10.1208/s12249-014-0126-7
In Vitro and In Vivo Performance of Dry Powder Inhalation Formulations: Comparison of Particles Prepared by Thin Film Freezing and Micronization
Yi-bo Wang (2014)
10.1016/J.IJPHARM.2019.06.006
Risk assessment and QbD based optimization of an Eprosartan mesylate nanosuspension: In-vitro characterization, PAMPA and in-vivo assessment.
Prachi B. Shekhawat (2019)
10.1517/17425247.2015.1057566
Effect of drug physico-chemical properties on the efficiency of top-down process and characterization of nanosuspension
T. Liu (2015)
10.3109/03639045.2012.654794
Development of stabilized itraconazole nanodispersions by using high-gravity technique
Z. Zhang (2012)
10.1016/j.xphs.2020.03.018
Intramacrophage delivery of dual drug loaded nanoparticles for effective clearance of Mycobacterium tuberculosis.
Priyanka Jahagirdar (2020)
10.32657/10356/68855
Synthesis of rough-surface carriers for dry powder inhalation
F. Zhang (2016)
10.3109/10717544.2012.742939
Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats
B. Du (2013)
10.1089/jamp.2014.1155
NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols.
W. Pornputtapitak (2015)
10.1007/s12281-014-0199-5
Recent Developments in Inhaled Triazoles Against Invasive Pulmonary Aspergillosis
R. Merlos (2014)
10.1016/j.jconrel.2012.03.013
Drug nanocrystals: In vivo performances.
L. Gao (2012)
10.1021/ACS.CGD.5B00349
Coamorphous Lurasidone Hydrochloride−Saccharin with Charge- Assisted Hydrogen Bonding Interaction Shows Improved Physical Stability and Enhanced Dissolution with pH-Independent Solubility Behavior
Shuai Qian (2015)
10.1016/j.ijpharm.2012.03.002
Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties.
C. Duret (2012)
10.1016/j.ijpharm.2014.05.045
Heat induced evaporative antisolvent nanoprecipitation (HIEAN) of itraconazole.
Naila A. Mugheirbi (2014)
10.1002/EJLT.201300368
Phospholipids in pulmonary drug delivery
N. Wauthoz (2014)
10.1021/CG200492W
Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals
N. J. Babu (2011)
10.1016/j.jconrel.2010.10.007
Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling.
Hany S M Ali (2011)
10.2147/IJN.S34091
New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
C. Duret (2012)
10.1016/S1875-5364(16)30090-5
Formulation of dried lignans nanosuspension with high redispersibility to enhance stability, dissolution, and oral bioavailability.
G. Shen (2016)
Small is big: Is Nanoamorphous Better than Amorphous Solid Dispersion and Nanocrystalline in Pharma?
Keat Theng Chow (2016)
10.1186/s42649-020-00032-9
Hot stage microscopy and its applications in pharmaceutical characterization
A. Kumar (2020)
10.1016/j.ijpharm.2013.05.013
Drug precipitation inhibitors in supersaturable formulations.
Sen Xu (2013)
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