The use of formulation technology to assess regional gastrointestinal drug absorption in humans

Basit, Abdul W.; Podczeck, Fridrun; Newton, JM; Waddington, W; Ell, Peter J.; Lacey, Larry F.

doi:10.1016/j.ejps.2003.10.003

Cited by 71 publications

(37 citation statements)

References 34 publications

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“…These differences may significantly influence the performance of drugs during their residence in the lower parts of the intestine. Unraveling the composition of colonic fluids led to better insights in colonic drug delivery strategies, resulting in pH-responsive and bacterially-triggered drug delivery technology (Basit et al, 2004(Basit et al, , 2009Ibekwe et al, 2008;McConnell et al, 2008;Vertzoni et al, 2010a), as well as optimized dissolution media to assess the performance of for instance colontargeted drug formulations in the lower intestine. These findings have led to the development of biorelevant fasted and fed state simulated colonic fluid (FaSSCoF and FeSSCoF, respectively), developed to mimic the fluids collected from the ascending colon in healthy adults (Vertzoni et al, 2010b).…”

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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“…However, the reported effects of formulation excipients on efflux inhibitors are not clearly defined, especially not in-vivo (Polli et al 2004). Furthermore, the effect on gastrointestinal transit by large amounts of sugars has been highlighted as another issue, especially for liquid formulations where large amounts of such excipients may be included (Adkin et al 1995;Yu et al 2002;Basit et al 2004).…”

Section: Biopharmaceutical Classification System (Bcs)mentioning

confidence: 99%

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension

Lennernäs

Abrahamsson

2005

Journal of Pharmacy and Pharmacology

184

119

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Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

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“…1D). No such bacterial metabolism has been observed for cimetidine or famotidine (Basit and Lacey, 2001;Basit et al, 2004), however. Treatment with antibiotics such as rifampicin decreases the absorption of ranitidine by decreasing the percentage of the total dose that disappears in the duodenal, jejunal, and ileal regions of the intestinal loops (Machavaram et al, 2006).…”

Section: N-oxide Reduction Of Drugsmentioning

confidence: 92%

Gut Microbiota-Mediated Drug-Antibiotic Interactions

Kim

2015

Drug Metab Dispos

109

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Xenobiotic metabolism involves the biochemical modification of drugs and phytochemicals in living organisms, including humans and other animals. In the intestine, the gut microbiota catalyzes the conversion of hydrophilic drugs into absorbable, hydrophobic compounds through hydroxyzation and reduction. Drugs and phytochemicals are transformed into bioactive (sulfasalazine, lovastatin, and ginsenoside Rb1), bioinactive (chloramphenicol, ranitidine, and metronidazole), and toxic metabolites (nitrazepam), thus affecting the pharmacokinetics of the original compounds.Antibiotics suppress the activities of drug-metabolizing enzymes by inhibiting the proliferation of gut microbiota. Antibiotic treatment might influence xenobiotic metabolisms more extensively and potently than previously recognized and reduce gut microbiotamediated transformation of orally administered drugs, thereby altering the systemic concentrations of intact drugs, their metabolites, or both. This review describes the effects of antibiotics on the metabolism of drugs and phytochemicals by the gut microbiota.

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The use of formulation technology to assess regional gastrointestinal drug absorption in humans

Cited by 71 publications

References 34 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

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension

Gut Microbiota-Mediated Drug-Antibiotic Interactions

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