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Article: Can low-dose combination products for inhalation be formulated in single crystalline particles?

TitleCan low-dose combination products for inhalation be formulated in single crystalline particles?
Authors
KeywordsCo-spray drying
Combination product
Inhaled corticosteroid (ICS)
Long-acting β2-agonist (LABA)
Mannitol
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejps
Citation
European Journal Of Pharmaceutical Sciences, 2010, v. 40 n. 1, p. 16-24 How to Cite?
AbstractThis study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and mannitol as a crystalline excipient. Two formulations comprising widely used ICS and LABA were studied: budesonide/formoterol fumarate dihydrate/mannitol (B/F/M-SD) and fluticasone propionate/salmeterol xinafoate/mannitol (F/S/M-SD). Various physicochemical properties of the powders were analyzed. Aerosol performance was evaluated by dispersing each powder from an Aerolizer® at 60 and 100L/min into a Next Generation Impactor. We obtained partially hollow spherical particles (volume median diameters of 2μm) with drug-enriched surfaces. Both formulations contained α-mannitol, and the ICSs were crystalline. The content of each drug component in the powder was found to conform to the theoretical dose. The ternary powders generated high fine particle fractions (>50% of the loaded dose), with concomitant drug deposition on the impactor stages. The aerosol performance of B/F/M-SD was maintained after storage over silica gel at 22°C for 11 weeks. In conclusion, co-spray dried particles of ICS/LABA/M-SD were largely crystalline, stable and showed excellent aerosol performance. They may provide an attractive alternative strategy to develop combination products without lactose blends. © 2010 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/141731
ISSN
2015 Impact Factor: 3.773
2015 SCImago Journal Rankings: 1.176
ISI Accession Number ID
Funding AgencyGrant Number
ICES
Science and Engineering Research Council of A*STAR, Singapore
Funding Information:

We thank the Electron Microscope Unit of the University of Sydney for tehnical support on SEM and XRD and Ms. Wang Zhan April of ICES for her help on XPS measurement. DH thanks both ICES and the Science and Engineering Research Council of A*STAR, Singapore for their financial support. This study was conducted as part of the special training program for MK supported by Daiichi-Sankyo Co., Ltd.

References

 

DC FieldValueLanguage
dc.contributor.authorKumon, Men_HK
dc.contributor.authorKwok, PCLen_HK
dc.contributor.authorAdi, Hen_HK
dc.contributor.authorHeng, Den_HK
dc.contributor.authorChan, HKen_HK
dc.date.accessioned2011-09-27T02:59:43Z-
dc.date.available2011-09-27T02:59:43Z-
dc.date.issued2010en_HK
dc.identifier.citationEuropean Journal Of Pharmaceutical Sciences, 2010, v. 40 n. 1, p. 16-24en_HK
dc.identifier.issn0928-0987en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141731-
dc.description.abstractThis study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and mannitol as a crystalline excipient. Two formulations comprising widely used ICS and LABA were studied: budesonide/formoterol fumarate dihydrate/mannitol (B/F/M-SD) and fluticasone propionate/salmeterol xinafoate/mannitol (F/S/M-SD). Various physicochemical properties of the powders were analyzed. Aerosol performance was evaluated by dispersing each powder from an Aerolizer® at 60 and 100L/min into a Next Generation Impactor. We obtained partially hollow spherical particles (volume median diameters of 2μm) with drug-enriched surfaces. Both formulations contained α-mannitol, and the ICSs were crystalline. The content of each drug component in the powder was found to conform to the theoretical dose. The ternary powders generated high fine particle fractions (>50% of the loaded dose), with concomitant drug deposition on the impactor stages. The aerosol performance of B/F/M-SD was maintained after storage over silica gel at 22°C for 11 weeks. In conclusion, co-spray dried particles of ICS/LABA/M-SD were largely crystalline, stable and showed excellent aerosol performance. They may provide an attractive alternative strategy to develop combination products without lactose blends. © 2010 Elsevier B.V.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpsen_HK
dc.relation.ispartofEuropean Journal of Pharmaceutical Sciencesen_HK
dc.subjectCo-spray dryingen_HK
dc.subjectCombination producten_HK
dc.subjectInhaled corticosteroid (ICS)en_HK
dc.subjectLong-acting β2-agonist (LABA)en_HK
dc.subjectMannitolen_HK
dc.titleCan low-dose combination products for inhalation be formulated in single crystalline particles?en_HK
dc.typeArticleen_HK
dc.identifier.emailKwok, PCL: pclkwok@hku.hken_HK
dc.identifier.authorityKwok, PCL=rp01540en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.ejps.2010.02.004en_HK
dc.identifier.pmid20172026-
dc.identifier.scopuseid_2-s2.0-77951207948en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951207948&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume40en_HK
dc.identifier.issue1en_HK
dc.identifier.spage16en_HK
dc.identifier.epage24en_HK
dc.identifier.isiWOS:000277553900003-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridKumon, M=23567119400en_HK
dc.identifier.scopusauthoridKwok, PCL=12646007800en_HK
dc.identifier.scopusauthoridAdi, H=24466627000en_HK
dc.identifier.scopusauthoridHeng, D=23766861200en_HK
dc.identifier.scopusauthoridChan, HK=7403402677en_HK
dc.identifier.citeulike6826024-

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