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Polymer Swelling, Drug Mobilization and Drug Recrystallization in Hydrating Solid Dispersion Tablets Studied by Multinuclear NMR Microimaging and Spectroscopy
KTH, Skolan för kemivetenskap (CHE), Kemi, Fysikalisk kemi.
KTH, Skolan för kemivetenskap (CHE), Kemi, Fysikalisk kemi.ORCID-id: 0000-0002-6524-1441
KTH, Skolan för kemivetenskap (CHE), Kemi, Fysikalisk kemi.ORCID-id: 0000-0002-0231-3970
2011 (Engelska)Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 8, nr 4, s. 1247-1256Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Despite the advantages offered by solid dispersions, the marketed products based on this technology are few. The most frequent concern is the stability of the amorphous drug. The state of the drug in solid dispersions is, in general, poorly characterized as the number of characterization techniques available to monitor nanometer-sized drug particles embedded in a matrix are limited. Here we present a combination of localized NMR spectroscopic and NMR imaging techniques which allow in situ monitoring of the state of the drug during tablet disintegration and dissolution. (19)F NMR relaxation is shown to be sensitive to both the crystalline/amorphous state and the size of the model nanoparticles made of the drug substance flutamide. The time course of drug mobilization and recrystallization is detected with spatial resolution within swelling solid dispersion tablets. Comparing results from spatially resolved (19)F, (2)H and (1)H NMR experiments, recrystallization is related to its enabling factors such as local hydration level and local mobility of the polymer matrix. The initially amorphous drug may recrystallize either by nanoparticle coalescence or by ripening of crystalline grains.

Ort, förlag, år, upplaga, sidor
2011. Vol. 8, nr 4, s. 1247-1256
Nyckelord [en]
recrystallization kinetics, amorphous drug nanoparticles, particle size, in situ monitoring, NMR imaging, hydroxypropyl methylcellulose HPMC
Nationell ämneskategori
Fysikalisk kemi
Identifikatorer
URN: urn:nbn:se:kth:diva-38974DOI: 10.1021/mp200051eISI: 000293307400026PubMedID: 21696185Scopus ID: 2-s2.0-79961049302OAI: oai:DiVA.org:kth-38974DiVA, id: diva2:438742
Forskningsfinansiär
VetenskapsrådetKnut och Alice Wallenbergs StiftelseTillgänglig från: 2011-09-05 Skapad: 2011-09-05 Senast uppdaterad: 2020-03-09Bibliografiskt granskad

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Dvinskikh, Sergey V.Furo, Istvan

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Dahlberg, CarinaDvinskikh, Sergey V.Furo, Istvan
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