Characterization of Human Duodenal Fluids in Fasted and Fed State Conditions

Riethorst, Danny; Mols, Raf; Duchateau, Guus; Tack, Jan; Brouwers, Joachim; Augustijns, Patrick

doi:10.1002/jps.24603

Cited by 208 publications

(234 citation statements)

References 43 publications

Supporting

Mentioning

226

Contrasting

Order By: Relevance

“…(Rao et al, 2010) This is probably due to the difference in composition of FaSSIF as compared to FaHIF. (Riethorst et al, 2015) Similar to the gastric fluids, a conversion of SV to SVA was observed. Nevertheless, SV appeared to be more stable in the intestinal fluids than in the gastric fluids.…”

Section: Dissolution Studymentioning

confidence: 85%

In vitro and in vivo investigation of the gastrointestinal behavior of simvastatin

Geboers

Stappaerts

Tack³

et al. 2016

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Simvastatin (SV) is marketed as a lactone ester prodrug which is hydrolyzed to the active simvastatin hydroxyacid (SVA). SV is characterized by a low solubility and undergoes extensive first-pass metabolism. In this study, the influence of the upper gastrointestinal environment on the intraluminal behavior of simvastatin was investigated by a series of in vitro experiments. Dissolution, stability and two-stage dissolution tests were performed using simulated and human gastrointestinal fluids. The dissolution studies revealed a relatively slow dissolution of SV as well as conversion of SV to SVA. The hydrolysis of SV was further examined and stability studies indicated a faster conversion in gastric fluids than in intestinal fluids. These isolated phenomena were then confirmed by the more integrative two-stage dissolution studies. To estimate the predictive value of the in vitro tests, an additional in vivo study was performed in which the gastrointestinal concentration-time profiles also revealed a slow dissolution of SV and faster degradation of SV to SVA in the stomach than in the intestinal tract. However, the plasma concentrations of SV and SVA did not directly correlate with the observed gastrointestinal concentrations, suggesting that gut wall and hepatic metabolism have a greater impact on systemic exposure of SV than the intraluminal interconversion between SV and SVA.

show abstract

Section: Dissolution Studymentioning

confidence: 85%

In vitro and in vivo investigation of the gastrointestinal behavior of simvastatin

Geboers

Stappaerts

Tack³

et al. 2016

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…The total bile salt concentration is kept at 3mM, and the lecithin concentration at 0.75mM, for direct comparison with the FaSSIF recipe. For mixed micelles with lecithin solution 1 (MWL-1), the bile salt composition is modified from that reported in literature, 22 with cholate and chenodeoxycholate bile salts being the predominant species in terms of hydroxylation. 23,24 A high degree of variability in bile salt composition in GI contents has been reported.…”

Section: Compositions Of the Biorelevant Testing Mediamentioning

confidence: 99%

“…23,24 A high degree of variability in bile salt composition in GI contents has been reported. 22,25 In an attempt to evaluate the impact of variability in bile salt composition on crystallization kinetics, mixed micelles with lecithin solution 2 (MWL-2) was also prepared. In MWL-2, the recipe was adjusted so that cholate and deoxycholate bile salts are the predominant species.…”

Section: Compositions Of the Biorelevant Testing Mediamentioning

confidence: 99%

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

Ormes

Lowinger

et al. 2017

CrystEngComm

View full text Add to dashboard Cite

Bile salts are endogenous surfactants present in the human gastrointestinal tract in the form of mixed micelles that also contain phospholipids. Due to the inevitable encounter of oral drug formulations with bile salts, it is important to understand the impact of bile salts on the crystallization tendency of poorly soluble compounds that form supersaturated solutions in vivo in order to maximize oral drug absorption. Although there has been an increasing number of studies focusing on the role of individual bile salts on drug crystallization, the effects of mixed micelles and biorelevant media composition on crystallization kinetics have only been studied to a limited extent. In this study, we evaluated the ability of binary and ternary bile salt combinations to maintain supersaturated aqueous solutions of telaprevir. Crystallization kinetics were also compared in more complex media that also contained the phospholipid, lecithin. These included fasted state simulated intestinal fluid (FaSSIF) (a widely used medium for formulation testing which contains a single bile salt, sodium taurocholate), and media that contained several endogenous bile salts. Finally, the combined effects of a polymer, hydroxypropylmethyl cellulose acetate succinate, and the testing media on crystallization kinetics were evaluated to provide insights into supersaturation formulation design. Solution bile salt composition was found to significantly influence crystallization kinetics. However, the presence of the polymer increased induction times sufficiently that differences between media were minimized. This study suggests that when evaluating the crystallization kinetics of systems with a propensity to undergo supersaturation in vivo, attention should be paid to selecting biorelevant media.

show abstract

“…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.…”

mentioning

confidence: 99%

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

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

(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...

show abstract

Characterization of Human Duodenal Fluids in Fasted and Fed State Conditions

Cited by 208 publications

References 43 publications

In vitro and in vivo investigation of the gastrointestinal behavior of simvastatin

In vitro and in vivo investigation of the gastrointestinal behavior of simvastatin

Compositional effect of complex biorelevant media on the crystallization kinetics of an active pharmaceutical ingredient

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

Contact Info

Product

Resources

About