Precipitation in and Supersaturation of Contents of the Upper Small Intestine After Administration of Two Weak Bases to Fasted Adults

Psachoulias, Dimitrios; Vertzoni, Maria; Goumas, Konstantinos; Kalioras, V.; Beato, Stefania; Butler, James

doi:10.1007/s11095-011-0506-6

Cited by 192 publications

(243 citation statements)

References 24 publications

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“…Aspiration of gastric and duodenal fluids in parallel with blood sampling resulted in new insights into how these enabling strategies behave after oral intake (Brouwers et al, 2006;Hens et al, 2015a;Stappaerts et al, 2015). Moreover, drug solubility measurements in these aspirated fluids can reveal whether the drug was supersaturated at the time of aspiration or directly started to precipitate (Hens et al, 2015b;Psachoulias et al, 2011;Van Den Abeele et al, 2015).…”

Section: Invasive Methodologiesmentioning

confidence: 99%

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

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(2017) Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities. International Journal of Pharmaceutics, 519 (1-2). pp. 79-97. ISSN 1873-3476Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/39960/1/FinalVersion-Revised-FOR_EPRINTS_1_YEAR_EMBARGO_ELSEVIER.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. After oral intake, a drug formulation is challenged by several gastrointestinal (GI) barriers. Complex variables such as pH, GI secretions and GI transit/motility along the GI tract can affect drug release and absorption in a positive or negative way depending on the physicochemical properties of the drug compound (e.g. pH/pKa interplay for ionizable drugs) and/or the formulation characteristics (e.g. pHsensitive coating). In addition, inter-subject variability in characteristics of the GI environment may cause variable drug absorption and systemic drug availability (Riethorst et al., 2015). Determining the median and range for specific GI variables, and understanding how they influence oral drug behavior along the GI tract, will be helpful in the field of drug development. 2The present review provides an overview of different methodologies that can be applied to study physiological variables of the human GI tract and their impact on oral drug absorption in healthy and patient populations. The methodologies have been subdivided into two groups: (i) noninvasive and (ii) invasive methodologies. Although some of the methodologies are more historical than operational, they have been of paramount importance for innovations in drug and formulation development; in addition, they have created the basis for several novel methodologies, leading to an in-depth comprehension of different GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and GI pH (intraluminal sampling and telemetry). Noninvasive methodologiesa. Scintigraphy Disturbances in the normal movement of food along the GI tract can be associated with abdominal pain, early satiety and nausea. Measurement of GI transit, es...

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Section: Invasive Methodologiesmentioning

confidence: 99%

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

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“…Despite substantial precipitation during in vitro lipolysis the bioavailability of halofantrine was not negatively affected after the administration of the same formulations to beagle dogs. Amorphous drug precipitation was recently shown for ketoconazole in intestinal aspirates (96). Assuming halofantrine precipitated also in an amorphous form in vivo, the rapid dissolution rate of the amorphous drug (as seen in vitro) could explain the retained bioavailability.…”

Section: Methods For the Characterisation Of The Drugmentioning

confidence: 93%

Characterising Lipid Lipolysis and Its Implication in Lipid-Based Formulation Development

Thomas

Holm

Rades

2012

AAPS J

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Abstract. Facing the increasing number of poorly water-soluble drugs, pharmaceutical scientists are required to break new grounds for the delivery of these pharmaceutically problematic drugs. Lipid-based drug delivery systems (LBDDS) have received increased interest as a novel drug delivery platform during the last decades and several successfully marketed products have shown the potential for LBDDS. However, there exists a discrepancy between the clear need for innovative delivery forms and their rational design. In the case of LBDDS, this can be attributed to the complexity of LBDDS after administration. Unlike conventional formulations, LBDDS are susceptible to digestion in the gastrointestinal tract, the interplay of delivery system, drug and physiology ultimately effecting drug disposition. In vitro lipolysis has become an important technique to mimic the enzymatic degradation. For the better understanding of how LBDDS promote drug delivery, in vitro lipolysis requires advanced characterisation methods. In this review, the physiological background of lipid digestion is followed by a thorough summary of the techniques that are currently used to characterise in vitro lipolysis. It would be desirable that the increasing knowledge about LBDDS will foster their rationale development thereby increasing their broader application.KEY WORDS: in vitro digestion; in vitro lipolysis models; lipid-based drug delivery systems; poorly soluble drugs; self-nanoemulsifying drug delivery systems (SNEDDS).

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“…Samples were selected and pooled so that the pooled sample had composition similar to the mean composition of intraluminal contents [5], HIFmean. In addition, samples were selected and pooled so that the pooled sample had composition similar to the median composition of intraluminal contents [5], HIFmedian ( Table 2). Due to multiple freeze -thawing processes, pH of both HIFmean and HIFmedian used in the solubility measurements was increased from 6.5 (aspiration time) to 7.5.…”

Section: Methodsmentioning

confidence: 99%

“…Data in simulated intestinal fluids were compared with data in human aspirates. Since it is not clear whether the average luminal composition should be considered on the basis of mean or of median luminal composition [5], in the present study two pooled aspirates samples that reflected the mean and the median luminal composition were used. …”

Section: Introductionmentioning

confidence: 99%

Increasing the biorelevance of simulated intestinal fluids for better predictions of drug equilibrium solubility in the fasted upper small intestine

Koumandrakis¹,

Vertzoni²,

Reppas³

2014

ADMET DMPK

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Precipitation in and Supersaturation of Contents of the Upper Small Intestine After Administration of Two Weak Bases to Fasted Adults

Abstract: Intralumenal precipitation of weakly alkaline, lipophilic, high permeability drugs may not be substantial. Estimating intestinal supersaturation in regard to free base is inadequate as other phases may precipitate.

Cited by 192 publications

References 24 publications

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Characterising Lipid Lipolysis and Its Implication in Lipid-Based Formulation Development

Increasing the biorelevance of simulated intestinal fluids for better predictions of drug equilibrium solubility in the fasted upper small intestine

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