| 1. |
- Asad, Shno, et al.
(författare)
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Inorganic nanoparticles for oral drug delivery : opportunities, barriers, and future perspectives
- 2022
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Ingår i: Current Opinion in Chemical Engineering. - : Elsevier. - 2211-3398. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- Oral delivery is the preferred route of drug administration due to patient compliance and convenience. Despite this, nanomedicines have so far primarily been developed for the parenteral route. Inorganic nanoparticles hold great promise as theranostics for oral drug delivery. This is gaining importance especially for the local treatment of gastrointestinal (GI) diseases. However, successful oral delivery of inorganic nanoparticles is challenged by complex physiological conditions in the GI tract. We discuss the main GI barriers and their impact on nanoparticle biotransformation and toxicity. An improved understanding of the complex interplay of inorganic nanoparticles with the dynamic GI environment can facilitate the development of efficient oral nanomedicines.
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| 2. |
- Eriksen, Jonas Borregaard, et al.
(författare)
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'Stirred not Shaken!' Comparing Agitation Methods for Permeability Studies Using a Novel Type of 96-Well Sandwich-Plates
- 2022
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 111:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- In order to achieve a high sample throughput, permeation experiments are often carried out using 96-well sandwich plates. Even though agitation is regarded as important, permeation studies in 96-well format are often carried out without agitation since orbital shaking, the most common agitation method for 96-well plates, has been reported to create difficulties (e.g., well-to-well cross-talk), and high cost and low availability limits the use of other agitation techniques (e.g., magnetic stirring). This study investigates how orbital shaking and magnetic stirring affect the apparent permeability of model compounds with different water-solubilities (methylene blue, carbamazepine, and albendazole) using a novel 96-well sandwich plate comprising a cellulose-hydrate membrane (PermeaPlain (R) plate). Orbital shaking was found less efficient than magnetic stirring in terms of homogeneously distributing a small volume of dye within the donor compartment. Furthermore, in terms of achieving maximum trans-barrier flux, magnetic stirring was found a more effective agitation method than orbital shaking. Obviously, with orbital shaking the medium in the bottom compartment of the sandwich plates never was mixed in-phase. The impact of insufficient mixing on permeation was found strongest with the most lipophilic compound, which correlates with literature reports that the contribution of the unstirred water layer towards the overall resistance of the barrier is most expressed in case of lipophilic drugs. Finally, it was tested how different liquid volumes in the bottom compartment of the plates affect the well-to-well cross-talk during permeation experiments under orbital shaking. This study revealed that 250-300 mu L should be used in the bottom compartment of the sandwich plates to reduce well-to-well cross-talk when using orbital shaking for agitation. (C) 2021 Published by Elsevier Inc. on behalf of American Pharmacists Association.
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| 3. |
- Jacobsen, Ann-Christin, et al.
(författare)
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Intrinsic lipolysis rate for systematic design of lipid-based formulations
- 2023
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Ingår i: Drug Delivery and Translational Research. - : Springer Nature. - 2190-393X .- 2190-3948. ; 13:5, s. 1288-1304
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key for the performance of LBFs and in vitro lipolysis is commonly used to compare the digestibility of LBFs. Results from in vitro lipolysis experiments depend highly on the experimental conditions and formulation characteristics, such as droplet size (which defines the surface area available for digestion) and interfacial structure. This study introduced the intrinsic lipolysis rate (ILR) as a surface area-independent approach to compare lipid digestibility. Pure acylglycerol nanoemulsions, stabilized with polysorbate 80 at low concentration, were formulated and digested according to a standardized pH–stat lipolysis protocol. A methodology originally developed to calculate the intrinsic dissolution rate of poorly water-soluble drugs was adapted for the rapid calculation of ILR from lipolysis data. The impact of surfactant concentration on the apparent lipolysis rate and lipid structure on ILR was systematically investigated. The surfactant polysorbate 80 inhibited lipolysis of tricaprylin nanoemulsions in a concentration-dependent manner. Coarse-grained molecular dynamics simulations supported these experimental observations. In the absence of bile and phospholipids, tricaprylin was shielded from lipase at 0.25% polysorbate 80. In contrast, the inclusion of bile salt and phospholipid increased the surfactant-free area and improved the colloidal presentation of the lipids to the enzyme, especially at 0.125% polysorbate 80. At a constant and low surfactant content, acylglycerol digestibility increased with decreasing acyl chain length, decreased esterification, and increasing unsaturation. The calculated ILR of pure acylglycerols was successfully used to accurately predict the IRL of binary lipid mixtures. The ILR measurements hold great promise as an efficient method supporting pharmaceutical formulation scientists in the design of LBFs with specific digestion profiles.
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| 4. |
- O'Shea, Joseph P., et al.
(författare)
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Best practices in current models mimicking drug permeability in the gastrointestinal tract - An UNGAP review
- 2022
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 170
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Forskningsöversikt (refereegranskat)abstract
- The absorption of orally administered drug products is a complex, dynamic process, dependant on a range of biopharmaceutical properties; notably the aqueous solubility of a molecule, stability within the gastrointestinal tract (GIT) and permeability. From a regulatory perspective, the concept of high intestinal permeability is intrinsically linked to the fraction of the oral dose absorbed. The relationship between permeability and the extent of absorption means that experimental models of permeability have regularly been used as a surrogate measure to estimate the fraction absorbed. Accurate assessment of a molecule's intestinal permeability is of critical importance during the pharmaceutical development process of oral drug products, and the current review provides a critique of in vivo, in vitro and ex vivo approaches. The usefulness of in silico models to predict drug permeability is also discussed and an overview of solvent systems used in permeability assessments is provided. Studies of drug absorption in humans are an indirect indicator of intestinal permeability, but both in vitro and ex vivo tools provide initial screening approaches and are important tools for assessment of permeability in drug development. Continued refinement of the accuracy of in silico approaches and their validation with human in vivo data will facilitate more efficient characterisation of permeability earlier in the drug development process and will provide useful inputs for integrated, end-to-end absorption modelling.
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