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45 results on '"Berthelsen, Ragna"'

36. Evaluating side‐by‐side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine.

Author

Eliasen, Jannik Nicklas, Berthelsen, Ragna, Slot, Anne Louise, and Müllertz, Anette

Subjects
*SUPERSATURATION, *DIFFUSION, *DRUG absorption, *PHARMACOLOGY, *ECOLOGY, *MONOMOLECULAR films
Abstract

Objective: To test whether a side‐by‐side diffusion model is suitable for studying drug supersaturation in an absorptive environment. Methods: The µD/P model and the µFLUX model, using a Caco‐2 cell monolayer/PAMPA membrane as the permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation–precipitation–permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution–permeation model, as compared to a simple dissolution model, were evaluated. Key findings: The two models produced similar results in terms of supersaturation, precipitation and permeation. The µFLUX model was considered more robust and easier to handle based on its cell‐free permeation system. Using the µFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation. Conclusion: The tested models were comparable; however, Caco‐2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug‐dependent effects of absorption on drug supersaturation. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Adding a Gastric Step to the Intestinal In VitroDigestion Model Improves the Prediction of Pharmacokinetic Data in Beagle Dogs of Two Lipid-Based Drug Delivery Systems

Author

Klitgaard, Mette, Beilles, Stephane, Sassene, Philip Jonas, Berthelsen, Ragna, and Müllertz, Anette

Abstract

Drug release from a lipid-based drug delivery system (LbDDS) is typically studied in vitrousing a one-step intestinal digestion model. However, lately the importance of incorporating gastric digestion has been stressed. The aim of the present study was to compare a two-step gastro-intestinal (GI) in vitrodigestion model to the commonly used one-step intestinal digestion model. The models were evaluated by studying release of the model drug A1260 from two LbDDSs (F-I and F-II), for which in vivopharmacokinetic data from oral administration to beagle dogs were available. The amount of A1260 recovered in the aqueous phases during and after the GI digestion of F-I and F-II was related to the Cmaxand AUC0–48hof the plasma concentration–time profiles of each formulation and produced a rank order in vitro–in vivo(IVIV) relation. In comparison, a similar IVIV rank ordering was obtained when relating the amount of A1260 recovered in the aqueous phase prior (t= 0 min), and following 15 min of intestinal digestion, to the plasma concentration–time profiles. However, after 60 min of intestinal digestion, the LbDDSs performed equally in the one-step in vitrodigestion model, contrary to what was observed in the two-step digestion model, and in vivo. As the GI digestion model produced a clearer distinction in terms of LbDDS rank ordering of the two LbDDSs, compared to the intestinal digestion model, it was found to be a promising in vitromodel to study and estimate the LbDDS behavior in vivo.

Published
2020
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44. Development of a μDissolution-Permeation model with in situdrug concentration monitoring

Author

Berthelsen, Ragna, Byrialsen, Julie Pelle, Holm, René, Jacobsen, Jette, Abrahamsson, Bertil, Saabye, Lasse, Madelung, Peter, and Müllertz, Anette

Abstract

The objective of the present study was to develop a combined dissolution-permeation model, compatible with the μDiss Profiler™ (μD/P model), to ensure continuous in situmonitoring of dissolved and permeated drug, respectively.

Published
2016
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45. The Influence of Temperature and Viscosity of Polyethylene Glycol on the Rate of Microwave-Induced In Situ Amorphization of Celecoxib.

Author

Hempel, Nele-Johanna, Dao, Tra, Knopp, Matthias M., Berthelsen, Ragna, Löbmann, Korbinian, and Angelov, Borislav

Subjects
AMORPHIZATION, POLYETHYLENE glycol, GLASS transition temperature, CELECOXIB, TEMPERATURE control, VISCOSITY, TEMPERATURE
Abstract

Microwaved-induced in situ amorphization of a drug in a polymer has been suggested to follow a dissolution process, with the drug dissolving into the mobile polymer at temperatures above the glass transition temperature (Tg) of the polymer. Thus, based on the Noyes–Whitney and the Stoke–Einstein equations, the temperature and the viscosity are expected to directly impact the rate and degree of drug amorphization. By investigating two different viscosity grades of polyethylene glycol (PEG), i.e., PEG 3000 and PEG 4000, and controlling the temperature of the microwave oven, it was possible to study the influence of both, temperature and viscosity, on the in situ amorphization of the model drug celecoxib (CCX) during exposure to microwave radiation. In this study, compacts containing 30 wt% CCX, 69 wt% PEG 3000 or PEG 4000 and 1 wt% lubricant (magnesium stearate) were exposed to microwave radiation at (i) a target temperature, or (ii) a target viscosity. It was found that at the target temperature, compacts containing PEG 3000 displayed a faster rate of amorphization as compared to compacts containing PEG 4000, due to the lower viscosity of PEG 3000 compared to PEG 4000. Furthermore, at the target viscosity, which was achieved by setting different temperatures for compacts containing PEG 3000 and PEG 4000, respectively, the compacts containing PEG 3000 displayed a slower rate of amorphization, due to a lower target temperature, than compacts containing PEG 4000. In conclusion, with lower viscosity of the polymer, at temperatures above its Tg, and with higher temperatures, both increasing the diffusion coefficient of the drug into the polymer, the rate of amorphization was increased allowing a faster in situ amorphization during exposure to microwave radiation. Hereby, the theory that the microwave-induced in situ amorphization process can be described as a dissolution process of the drug into the polymer, at temperatures above the Tg, is further strengthened. [ABSTRACT FROM AUTHOR]

Published
2021
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