| 1. |
- Adler, Camille, et al.
(författare)
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Flow-through cross-polarized imaging as a new tool to overcome the analytical sensitivity challenges of a low-dose crystalline compound in a lipid matrix
- 2015
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 115, s. 20-30
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Tidskriftsartikel (refereegranskat)abstract
- Assessing the physical state of a low-dose active compound in a solid lipid or polymer matrix is analytically challenging, especially if the matrix exhibits some crystallinity. The aim of this study was first to compare the ability of current methods to detect the presence of a crystalline model compound in lipid matrices. Subsequently, a new technique was introduced and evaluated because of sensitivity issues that were encountered with current methods. The new technique is a flow-through version of cross-polarized imaging in transmission mode. The tested lipid-based solid dispersions (SDs) consisted of beta-carotene (BC) as a model compound, and of Gelucire 50/13 or Geleol mono- and diglycerides as lipid matrices. The solid dispersions were analyzed by (hyper) differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and microscopic techniques including atomic force microscopy (AFM). DSC and XRPD could analyze crystalline BC at concentrations as low as 3% (w/w) in the formulations. However, with microscopic techniques crystalline particles were detected at significantly lower concentrations of even 0.5% (w/w) BC. A flow-through cross-polarized imaging technique was introduced that combines the advantage of analyzing a larger sample size with high sensitivity of microscopy. Crystals were detected easily in samples containing even less than 0.2% (w/w) BC. Moreover, the new tool enabled approximation of the kinetic BC solubility in the crystalline lipid matrices. As a conclusion, the flow-through cross-polarized imaging technique has the potential to become an indispensable tool for characterizing low-dose crystalline compounds in a lipid or polymer matrix of solid dispersions. (C) 2015 Elsevier B.V. All rights reserved.
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| 2. |
- Adler, Camille, et al.
(författare)
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Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 499:1-2, s. 90-100
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Tidskriftsartikel (refereegranskat)abstract
- Amorphous solid dispersions have for many years been a focus in oral formulations, especially in combination with a hot-melt extrusion process. The present work targets a novel approach with a system based on a fatty acid, a polymer and an inorganic carrier. It was intended to adsorb the acidic lipid by specific molecular interactions onto the solid carrier to design disorder in the alkyl chains of the lipid. Such designed lipid microdomains (DLM) were created as a new microstructure to accommodate a compound in a solid dispersion. Vibrational spectroscopy, X-ray powder diffraction, atomic force microscopy as well as electron microscopic imaging were employed to study a system of stearic acid, hydroxypropylcellulose and aluminum magnesium silicate. beta-carotene was used as a poorly water-soluble model substance that is difficult to formulate with conventional solid dispersion formulations. The results indicated that the targeted molecular excipient interactions indeed led to DLMs for specific compositions. The different methods provided complementary aspects and important insights into the created microstructure. The novel delivery system appeared to be especially promising for the formulation of oral compounds that exhibit both high crystal energy and lipophilicity. (C) 2015 Elsevier B.V. All rights reserved.
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| 3. |
- Adler, Camille, et al.
(författare)
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Multifractal and mechanical analysis of amorphous solid dispersions
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 523:1, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- The formulation of lipophilic and hydrophobic compounds is a challenge for the pharmaceutical industry and it requires the development of complex formulations. Our first aim was to investigate hot-melt extrudate microstructures by means of multifractal analysis using scanning electron microscopy imaging. Since the microstructure can affect solid dosage form performance such as mechanical properties, a second objective was to study the influence of the type of adsorbent and of the presence of an amorphous compound on extrudate hardness. β-Carotene (BC) was chosen as poorly water-soluble model compound. Formulations containing a polymer, a lipid and two different silica based inorganic carriers were produced by hot-melt extrusion. Based on scanning electron microscopy/energy dispersive X-ray spectroscopy, the obtained images were analyzed using multifractal formalism. The breaking force of the strands was assessed by a three point bending test. Multifractal analysis and three point bending results showed that the nature of interparticle interactions in the inorganic carrier as well as the presence of amorphous BC had an influence on the microstructure and thus on the mechanical performance. The use of multifractal analysis and the study of the mechanical properties were complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.
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| 4. |
- Adler, Camille, et al.
(författare)
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Multifractal Characterization of Pharmaceutical Hot-Melt Extrudates.
- 2017
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 34:2, s. 321-332
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Multifractal geometry has become a powerful tool to describe complex structures in many fields. Our first aim was to combine imaging and multifractal analysis to better understand the microstructure of pharmaceutical extrudates. A second objective was to study erosion/dispersion behavior of the formulations because it would condition release of any drug.METHODS: Different formulations containing a lipid, a polymer and different silica based inorganic carriers were produced by hot-melt extrusion at various screw speeds. Multifractal analysis was based on scanning electron microscopy/energy dispersive X-Ray spectroscopy images. This microstructural analysis was complemented with dynamic optical imaging of formulation erosion/dispersion behavior.RESULTS: Multifractal analysis indicated that inorganic carrier type and concentration as well as the screw speed affected the microstructure of the extrudates. The aqueous erosion/dispersion study showed that only the type and concentration of inorganic carrier were important.CONCLUSIONS: The use of microstructural and dispersion analysis appeared to be complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.
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| 5. |
- Alison, Lauriane, et al.
(författare)
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Emulsions Stabilized by Chitosan-Modified Silica Nanoparticles : pH Control of Structure-Property Relations
- 2018
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 34:21, s. 6147-6160
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Tidskriftsartikel (refereegranskat)abstract
- In food-grade emulsions, particles with an appropriate surface modification can be used to replace surfactants and potentially enhance the stability of emulsions. During the life cycle of products based on such emulsions, they can be exposed to a broad range of pH conditions and hence it is crucial to understand how pH changes affect stability of emulsions stabilized by particles. Here, we report on a comprehensive study of the stability, microstructure, and macroscopic behavior of pH-controlled oil-in-water emulsions containing silica nanoparticles modified with chitosan, a food-grade polycation. We found that the modified colloidal particles used as stabilizers behave differently depending on the pH, resulting in unique emulsion structures at multiple length scales. Our findings are rationalized in terms of the different emulsion stabilization mechanisms involved, which are determined by the pH-dependent charges and interactions between the colloidal building blocks of the system. At pH 4, the silica particles are partially hydrophobized through chitosan modification, favoring their adsorption at the oil-water interface and the formation of Pickering emulsions. At pH 5.5, the particles become attractive and the emulsion is stabilized by a network of agglomerated particles formed between the droplets. Finally, chitosan aggregates form at pH 9 and these act as the emulsion stabilizers under alkaline conditions. These insights have important implications for the processing and use of particle-stabilized emulsions. On one hand, changes in pH can lead to undesired macroscopic phase separation or coalescence of oil droplets. On the other hand, the pH effect on emulsion behavior can be harnessed in industrial processing, either to tune their flow response by altering the pH between processing stages or to produce pH-responsive emulsions that enhance the functionality of the emulsified end products.
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| 6. |
- Alison, Lauriane, et al.
(författare)
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Pickering and Network Stabilization of Biocompatible Emulsions Using Chitosan-Modified Silica Nanoparticles
- 2016
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:50, s. 13446-13457
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Tidskriftsartikel (refereegranskat)abstract
- Edible solid particles constitute an attractive alternative to surfactants as stabilizers of food-grade emulsions for products requiring a long-term shelf life. Here, we report on a new approach to stabilize edible emulsions using silica nanoparticles modified by noncovalently bound chitosan oligomers. Electrostatic modification with chitosan increases the hydrophobicity of the silica nanoparticles and favors their adsorption at the oil water interface. The interfacial adsorption of the chitosan-modified silica particles enables the preparation of oil-in-water emulsions with small droplet sizes of a few micrometers through high-pressure homogenization. This approach enables the stabilization of food-grade emulsions for more than 3 months. The emulsion structure and stability can be effectively tuned by controlling the extent of chitosan adsorption on the silica particles. Bulk and interfacial rheology are used to highlight the two stabilization mechanisms involved. Low chitosan concentration (1 wt % with respect to silica) leads to the formation of a viscoelastic film of particles adsorbed at the oil water interface, enabling Pickering stabilization of the emulsion. By contrast, a network of agglomerated particles formed around the droplets is the predominant stabilization mechanism of the emulsions at higher chitosan content (5 wt % with respect to silica). These two pathways against droplet coalescence and coarsening open up different possibilities to engineer the long-term stabilization of emulsions for food applications.
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| 10. |
- Ansari, Shaquib Rahman, 1993-
(författare)
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From design to application: Iron oxide nanoparticles for imaging and therapeutics in inflammatory and infectious diseases
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising advancement in nanomedicine, demonstrating remarkable potential in both diagnostic and therapeutic applications. They can be magnetized in a magnetic field and do not show permanent magnetization, allowing precise localization within the body. Under an alternating magnetic field, SPIONs generate heat, which can be used for magnetic hyperthermia therapy against cancer or to trigger drug release. Diagnostically, they are widely used as contrast agents for magnetic resonance imaging (MRI), while magnetic particle imaging (MPI) is an emerging preclinical diagnostic technique using SPIONs as tracers.Despite these promising applications, the clinical utility of SPIONs is hindered by challenges related to scalable and reproducible manufacturing. Focused efforts are also needed to improve MPI resolution. Moreover, the application of magnetic hyperthermia for treating inflammatory and infectious conditions remains relatively underexplored. Therefore, the primary objective of this thesis was to develop SPIONs tailored for imaging and therapy of inflammatory and infectious diseases through scalable manufacturing techniques. The first part of the study involved a systematic review to examine the most pertinent research on use of SPIONs for diagnosing and treating chronic inflammatory diseases. MRI was identified as the predominant application of SPIONs. However, there was limited exploration of MPI and magnetic hyperthermia for imaging and treating inflammatory diseases, respectively.In the second project, a risk-based pharmaceutical quality by design approach was used to optimize SPIONs for magnetic hyperthermia. The effect of nanoparticle properties on MPI performance was systematically investigated in the third project. Additionally, these projects established flame spray pyrolysis as a scalable and reproducible technique, for synthesizing nanoparticles with complex stoichiometry for magnetic hyperthermia and MPI.In final part of the study, SPIONs were incorporated into composites by scalable techniques, to improve the treatment of inflammatory and infectious diseases. SPIONs were incorporated in tablets with an anti-inflammatory drug, celecoxib. The drug solubility improved significantly through magnetic hyperthermia-induced in situ amorphization. SPIONs were also incorporated into microfibers, and heat dissipation from magnetic microfibers was used with doxycycline against methicillin-resistant Staphylococcus aureus. This resulted in substantial reduction in bacterial growth compared to using the drug alone.This thesis introduced systematic exploration of SPION properties and their functional performance, established a scalable synthesis technique for their production, and developed novel systems for wider adaptation of SPIONs in biomedical applications.
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