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Structure and mobility of lactose in lactose/sodium montmorillonite nanocomposites
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Department of Chemistry, Umeå University.
School of Pharmacy, University of East Anglia.
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(English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827Article in journal (Refereed) Submitted
Abstract [en]

This study aims at investigating the molecular level organization and molecular mobility in montmorillonite nanocomposites with the uncharged organic low molecular weight compound lactose commonly used in pharmaceutical drug delivery, food technology, and flavoring. Nanocomposites were prepared under slow and fast drying conditions, attained by drying at ambient conditions and by spray-drying, respectively. A detailed structural investigation was performed with modulated differential scanning calorimetry, powder X-ray diffraction, solid-state nuclear magnetic resonance, scanning electron microscopy, microcalorimetry, and molecular dynamic simulations. The lactose was intercalated in the sodium montmorillonite interlayer space regardless of the clay content, drying rate, or humidity exposure. Although, the spray-drying resulted in higher proportion of intercalated lactose compared with the drying under ambient conditions, non-intercalated lactose was present at 20 wt% lactose content. This indicates limitations in maximum load capacity of nonionic organic substances into the montmorillonite interlayer space. Furthermore, a fraction of the intercalated lactose in the co-spray-dried nanocomposites diffused out from the clay interlayer space upon humidity exposure. Also, the lactose in the nanocomposites demonstrated higher molecular mobility than that of neat amorphous lactose. This study provides a foundation for understanding functional properties of nanocomposites, such as loading capacity and physical stability.

National Category
Materials Chemistry
URN: urn:nbn:se:uu:diva-300158OAI: oai:DiVA.org:uu-300158DiVA: diva2:951079
Available from: 2016-08-05 Created: 2016-08-03 Last updated: 2016-09-02Bibliographically approved
In thesis
1. Pharmaceutical Nanocomposites: Structure–Mobility–Functionality Relationships in the Amorphous State
Open this publication in new window or tab >>Pharmaceutical Nanocomposites: Structure–Mobility–Functionality Relationships in the Amorphous State
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amorphous materials are found in pharmaceutical formulations both as excipients and active ingredients. Indeed, these formulations are becoming an essential strategy for incorporating drugs into well-performing solid dosage forms. However, there is an unmet need of better understanding of the microstructure and component interactions in amorphous formulations to be able to design materials with improved functionalities. The aim of this thesis is to give deepened knowledge about structure-mobility-functionality relationships in amorphous for-mulations by studying composites produced from sugars and filler particles. The structure, the mobility, and physical stability of the composite materials were studied using calorimetry, X-ray diffraction, microscopy, spectroscopy, and molecular dynamics simulations. Further, the moisture sorption of the composites was determined with dynamic vapor sorption. The compression mechanics of the composites was evaluated with compression analysis.

It was demonstrated that fillers change the overall properties of the amorphous material. Specifically, the physical stability of the composite was by far improved compared to the amorphous sugar alone. This effect was pronounced for formulations with 60 wt% filler content or more. Amorphous lactose that normally recrystallizes within a few minutes upon humidity exposure, could withstand recrystallization for several months at 60% RH in composites with 80 wt% cellulose nanocrystals (CNC) or sodium montmorillonite (Na-MMT). The increased physical stability of the amorphous sugars was related to intra-particle confinement in extra-particle voids formed by the fillers and to immobilization of the amorphous phase at the surface of the fillers. Also, the composite formation led to increased particle hardness for the lactose/CNC and the lactose/Na-MMT nanocomposites. The largest effect on particle hardness was seen with 40-60 wt% nanofiller and could be related to skeleton formation of the nanofillers within the composite particles. The hygroscopicity for the lactose/Na-MMT nanocomposites decreased as much as 47% compared to ideal simple mixtures of the neat components. The nanofillers did not influence the water sorption capacity in the amorphous domains; however, lactose (intercalated into Na-MMT) interacted with the sodium ions in the interlayer space which led to the lowered hygroscopicity of this phase.

The thesis advanced the knowledge of the microstructure of amorphous pharmaceutical com-posites and its relationship with pharmaceutical functionalities. It also presented new approaches for stabilizing the amorphous state by using fillers. The concept illustrated here might be used to understand similar phenomena of stabilization of amorphous formulations.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 79 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 220
amorphous, pharmaceutical composites, solid state, structure, molecular mobility, spray-drying, freeze-drying, moisture sorption, physical stability, compression
National Category
Materials Chemistry
Research subject
Pharmaceutical Science
urn:nbn:se:uu:diva-300159 (URN)978-91-554-9642-5 (ISBN)
External cooperation:
Public defence
2016-09-23, B21, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2016-08-31 Created: 2016-08-03 Last updated: 2016-09-05

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