Show simple item record

dc.contributor.authorRamachandran, Vasuki
dc.contributor.authorMurnane, Darragh
dc.contributor.authorHammond, Robert B.
dc.contributor.authorPickering, Jonathan
dc.contributor.authorRoberts, Kevin J.
dc.contributor.authorSoufian, Majeed
dc.contributor.authorForbes, Ben
dc.contributor.authorJaffari, Sara
dc.contributor.authorMartin, Gary P.
dc.contributor.authorCollins, Elizabeth
dc.contributor.authorPencheva, Klimentina
dc.date.accessioned2015-02-05T11:18:06Z
dc.date.available2015-02-05T11:18:06Z
dc.date.issued2015-01-05
dc.identifier.citationRamachandran , V , Murnane , D , Hammond , R B , Pickering , J , Roberts , K J , Soufian , M , Forbes , B , Jaffari , S , Martin , G P , Collins , E & Pencheva , K 2015 , ' Formulation pre-screening of inhalation powders using computational atom-atom systematic search method ' , Molecular Pharmaceutics , vol. 12 , no. 1 , pp. 18-33 . https://doi.org/10.1021/mp500335w
dc.identifier.issn1543-8384
dc.identifier.otherPURE: 8052453
dc.identifier.otherPURE UUID: 7e6a6d9d-414a-43ed-b649-d7a0adaa6f22
dc.identifier.otherScopus: 84920274322
dc.identifier.otherWOS: 000347506300003
dc.identifier.urihttp://hdl.handle.net/2299/15351
dc.descriptionThis is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
dc.description.abstractThe synthonic modeling approach provides a molecule-centered understanding of the surface properties of crystals. It has been applied extensively to understand crystallization processes. This study aimed to investigate the functional relevance of synthonic modeling to the formulation of inhalation powders by assessing cohesivity of three active pharmaceutical ingredients (APIs, fluticasone propionate (FP), budesonide (Bud), and salbutamol base (SB)) and the commonly used excipient, α-lactose monohydrate (LMH). It is found that FP (-11.5 kcal/mol) has a higher cohesive strength than Bud (-9.9 kcal/mol) or SB (-7.8 kcal/mol). The prediction correlated directly to cohesive strength measurements using laser diffraction, where the airflow pressure required for complete dispersion (CPP) was 3.5, 2.0, and 1.0 bar for FP, Bud, and SB, respectively. The highest cohesive strength was predicted for LMH (-15.9 kcal/mol), which did not correlate with the CPP value of 2.0 bar (i.e., ranking lower than FP). High FP-LMH adhesive forces (-11.7 kcal/mol) were predicted. However, aerosolization studies revealed that the FP-LMH blends consisted of agglomerated FP particles with a large median diameter (∼4-5 μm) that were not disrupted by LMH. Modeling of the crystal and surface chemistry of LMH identified high electrostatic and H-bond components of its cohesive energy due to the presence of water and hydroxyl groups in lactose, unlike the APIs. A direct comparison of the predicted and measured cohesive balance of LMH with APIs will require a more in-depth understanding of highly hydrogen-bonded systems with respect to the synthonic engineering modeling tool, as well as the influence of agglomerate structure on surface-surface contact geometry. Overall, this research has demonstrated the possible application and relevance of synthonic engineering tools for rapid pre-screening in drug formulation and design.en
dc.format.extent16
dc.language.isoeng
dc.relation.ispartofMolecular Pharmaceutics
dc.rightsOpen
dc.subjectbudesonide
dc.subjectde-agglomeration
dc.subjectfluticasone propionate
dc.subjectin silico formulation design
dc.subjectinhalation drug delivery
dc.subjectinter-particle interaction
dc.subjectlaser diffraction
dc.subjectmolecular and synthonic modeling
dc.subjectpowder dispersion analysis
dc.subjectsalbutamol
dc.subjectα-lactose monohydrate
dc.subjectPharmaceutical Science
dc.subjectMolecular Medicine
dc.subjectDrug Discovery
dc.titleFormulation pre-screening of inhalation powders using computational atom-atom systematic search methoden
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionCentre for Research into Topical Drug Delivery and Toxicology
dc.contributor.institutionPharmaceutics
dc.contributor.institutionAirway Group
dc.contributor.institutionPharmaceutical Analysis and Product Characterisation
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2015-01-05
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1021/mp500335w
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record