Use of conventional surfactant media as surrogates for FaSSIF in simulating in vivo dissolution of BCS class II drugs

Lehto, Paula; Kortejärvi, Hanna; Liimatainen, Anni; Ojala, K.; Kangas, Heli; Hirvonen, Jouni; Tanninen, Veli Pekka; Peltonen, Leena

doi:10.1016/j.ejpb.2011.02.007

Cited by 39 publications

(22 citation statements)

References 24 publications

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“…The absorption process of oral dosage forms through the whole gastro-intestinal tract can be described by the transit compartment model (Kagan & Hoffman, 2008;Lehto et al, 2011). Owing to the closeness to the real process, the transit compartment model is a better choice to estimate drug oral absorption rather than the simple first-order rate constant.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics,in vitroandin vivocorrelation, and efficacy of exenatide microspheres in diabetic rats

Zhao

et al. 2014

Drug Delivery

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Modeling and simulation are aimed at achieving information about the behaviors of the drugs without the actual measurements and determination. The purpose of this study was to characterize the in vivo behavior of exenatide microspheres using model-based methods. Exenatide is a glucagon-like peptide-1 agonist medication, belonging to the group of incretin mimetics, approved for the treatment of diabetes mellitus type 2. An oil-in-water solvent evaporation method was used to prepare the exenatide microspheres and their physicochemical features were investigated. After subcutaneous injection of exenatide microspheres to streptozotocin-induced diabetic rats, the exenatide concentrations increased and kept increasing and the blood glucose decreased in all diabetic rats. The in vivo release behavior of exenatide from microspheres was described by a transit compartment model. Based on the transit compartment model, the simulation method was proposed for the description of in vivo release. The in vitro and in vivo correlation (IVIVC) was established by the model-based simulation (R(2) = 0.903) and deconvolution (R(2) = 0.922) methods successfully. Using a transit compartment model to characterize the in vivo exenatide release from microspheres is an acceptable approach, and the IVIVC can be estimated reliably with the model-based simulation method.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics,in vitroandin vivocorrelation, and efficacy of exenatide microspheres in diabetic rats

Zhao

et al. 2014

Drug Delivery

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“…At the same time, the occurrence of increasingly lipophilic and less water soluble drugs requested the development of alternative dissolution media. Various additives have been suggested as they facilitate the wetting of solids and the solubilisation of lipophilic drugs into micelles (Kimura et al, 1972;Kleberg et al, 2010b;Lehto et al, 2011;Persson et al, 2005;Schwebel et al, 2011). A general expectation is that such media mimic the in vivo dissolution process more closely than simple buffers.…”

Section: Introductionmentioning

confidence: 99%

Application of simulated intestinal fluid on the phospholipid vesicle-based drug permeation assay

Fischer¹,

Kirchmeyer²,

Fricker³

et al. 2012

International Journal of Pharmaceutics

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The compatibility of fasted state simulated intestinal fluid (FaSSIF) in drug permeation studies employing the phospholipid vesicle-based permeation assay (PVPA) model was confirmed by a set of different integrity indicators. Neither calcein permeability nor electrical resistance were found significantly changed indicating unaffected barrier tightness. Furthermore, the release of phospholipid from the barriers in contact with FaSSIF was negligible, although sodium taurocholate disappeared from the donor - possibly due to transfer into the barrier. Visual examination of the barrier structure by confocal laser scanning microscopy (CLSM) revealed no changes. The model drugs, cimetidine, nadolol, ketoprofen and griseofulvin showed either slightly enhanced or unchanged permeability values in the presence of FaSSIF. This may be attributed to micellar encapsulation and/or slight changes in barrier characteristics. Particularly for poorly soluble drugs, FaSSIF appeared favourable in terms of markedly improved recovery. Moreover, utilisation of BSA in the receiver compartment seems to augment this beneficial effect on recovery rate. It is likely that this experimental set-up affords better sink conditions in the receiver phase, which results in higher fluxes. Overall, a combination of FaSSIF in the donor phase and BSA in the receiver phase facilitates improved experimental output.

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“…Surface properties of biorelevant media have been studied [21]; however, little attention It has been previously observed using a set of reference compounds that ionized acidic compounds showed, in general, lower SE than ionized bases. It was suggested that the solubility of ionized acids was not increased in FaSSIF due to electrostatic repulsions with the net negatively charged FaSSIF media components [8].…”

Section: Discussionmentioning

confidence: 99%

Importance of Critical Micellar Concentration for the Prediction of Solubility Enhancement in Biorelevant Media

2015

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This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF). The solubility of 51 chemically diverse compounds was measured in FaSSIF and in phosphate buffer and the surface activity parameters were determined. This study showed that the compound critical micellar concentration parameter (CMC) correlates strongly with the solubility enhancement (SE) observed in FaSSIF compared to phosphate buffer. Thus, the intrinsic capacity of molecules to form micelles is also a determinant for each compound's affinity to the micelles of biorelevant surfactants. CMC correlated better with SE than lipophilicity (logD), especially over the logD range typically covered by drugs (2 < logD < 4). CMC can become useful to guide drug discovery scientists to better diagnose, improve, and predict solubility in biorelevant media, thereby enhancing oral bioavailability of drug candidates.

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Use of conventional surfactant media as surrogates for FaSSIF in simulating in vivo dissolution of BCS class II drugs

Cited by 39 publications

References 24 publications

Pharmacokinetics,in vitroandin vivocorrelation, and efficacy of exenatide microspheres in diabetic rats

Pharmacokinetics,in vitroandin vivocorrelation, and efficacy of exenatide microspheres in diabetic rats

Application of simulated intestinal fluid on the phospholipid vesicle-based drug permeation assay

Importance of Critical Micellar Concentration for the Prediction of Solubility Enhancement in Biorelevant Media

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