Designing a Dynamic Dissolution Method: A Review of Instrumental Options and Corresponding Physiology of Stomach and Small Intestine

Čulen, Martin; Rezácová, A; Jampílek, Josef; Dohnal, Jiří

doi:10.1002/jps.23494

Cited by 40 publications

(28 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Small intestinal manometry GI motility and the associated migrating motor or myoelectric complex (MMC) play a crucial role in transporting ingested material from the stomach through the intestine and into the colon by means of segmental and peristaltic contractions (Cannon, 1912;Deloose et al, 2012). The propagating wave of peristalsis is regulated by hormones, paracrine signaling, and the autonomic nervous system, while segmentation is carried out by longitudinal muscle relaxation and circular muscle contraction thereby mixing GI contents with digestive enzymes and ensuring composition uniformity and sufficient epithelial contact for absorption (Culen et al, 2013). The GE rate is controlled by gastric distention promoting emptying and intestinal stimuli slowing emptying (Hunt, 1963).…”

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

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

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

View full text Add to dashboard Cite

show abstract

“…An understanding of all these physiological parameters can serve as a basis for designing dissolution testing methods and systems that can more fully represent the GI tract in humans and allow more IVIVC to be obtained, thus improving the oral bioperformance of dosage forms [65]. Currently, none of the guidance or international pharmacopoeias describes media to simulate food effects.…”

Section: Dissolution Mediamentioning

confidence: 99%

“…This is depicted as Equation The four types of compendial dissolution apparatuses used for testing the oral dosage forms include the USP I (basket) and the USP II (paddle) apparatuses which can be successfully used for QC purposes, such as lot-to-lot quality testing [65]. These methods, however, are not physiologically relevant as they use large volume of media (500 -1000 ml), enable the use of one dissolution medium at a time and have hydrodynamics that do not resemble the GI tract [51,65]. Several studies have investigated the flow pattern of the dissolution apparatuses USP I (basket) and USP II (paddle) at various speeds by using computational fluid dynamics [131].…”

Section: Dissolution Apparatusesmentioning

confidence: 99%

“…The other two compendial dissolution apparatuses are the USP III (reciprocating cylinder, Bio-Dis) and IV (flow-through cell) which offer the advantages of determining release from the dosage form under various, consecutive conditions simulating the GI physiology. The release experiments performed with Bio-Dis and flow-through cell can be set up with a series of dissolution media in one single run, thus making it possible to mimic the "history" of the dosage form as it passes through the GI tract and to generate an IVIVC on an a priori basis [65,82,138,139]. The USP III apparatus provides a means of stepping through different buffers and has been reported to be a very useful technique for extended release dosage forms [138][139][140].…”

Section: Dissolution Apparatusesmentioning

confidence: 99%

“…Also, pH was also not raised back to the original value as it was maintained only by the action of the contained buffer. In the second apparatus, however, pH, volume and the composition of the duodenal fluid were all left without intervention [65,148]. Psachoulias et al [149] presented an improved method, where although a gastric and a duodenal compartment were used, the dilution of the duodenal fluid which was the FaSSIF V2 plus was compensated by an inflow of a concentrated medium from a third vessel.…”

Section: Dissolution Apparatusesmentioning

confidence: 99%

See 2 more Smart Citations

Drug release from matrix tablets: physiological parameters and the effect of food

Nokhodchi

Asare-Addo

2014

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction: As dissolution plays an important and vital role in the drug-delivery process of oral solid dosage forms, it is, therefore, essential to critically evaluate the parameters that can affect this process. Areas covered:The consumption of food as well as the physiological environment and properties of the gastrointestinal tract, such as its volume and composition of fluid, the fluid hydrodynamics, properties of the intestinal membrane, drug dose and solubility, pK a , diffusion coefficient, permeability and particle size, all affect drug dissolution and absorption rate. There are several dissolution approaches that have been developed to address the conditions as experienced in the in vivo environment, as the traditional dissolution being a quality control method is not biorelevant and as such do not always produce meaningful data. This review also describes the development of a systematic way that differentiates between robust and non-robust formulations by varying the effects of agitation and ionic strength through the use of the automated United States Pharmacopeia type III Bio-Dis apparatus. Expert opinion:With the improved understanding of the physiological parameters that can affect the oral bioperformance of dosage forms, strides have, therefore, been made in making dissolution testing methods more bio-logically based with the view of obtaining more in vitro--in vivo correlations.Keywords: agitation rate, biodissolution, drug release, effect of food, hydrophilic matrices, ionic strength Highlights -Understanding all the physiological parameters can serve as a basis for designing dissolution testing methods and systems that can more fully represent the gastrointestinal (GI) tract in humans and allow more in vitro-in vivo (IVIVC) correlations to be obtained thereby improving the oral bioperformance of dosage forms.-Simulation of GI conditions is essential to adequately predict the in vivo behaviour of drug formulations.-The choice of appropriate media for in vitro tests is crucial to their ability to correctly forecast the food effect in pharmacokinetic studies.-Several methods of dissolution testing have been conducted and are still ongoing that seek to further understand and develop media and dissolution methods to better represent the in vivo conditions and to aid in the better prediction of in vivo drug release.-Systematic change of agitation method and ionic strength evaluation may be used as additional tools in allowing for the identification of potential fed and fasted effects on drug release from hydrophilic matrices in the drive for developing dissolution methodologies that are more relevant in helping to achieve more IVIVC.

show abstract

Supersaturation and Precipitation of Posaconazole Upon Entry in the Upper Small Intestine in Humans

Hens

Brouwers

Corsetti

et al. 2016

Journal of Pharmaceutical Sciences

104

View full text Add to dashboard Cite

The purpose of this study was to explore gastrointestinal dissolution, supersaturation and precipitation of the weakly basic drug posaconazole in humans, and to assess the impact of formulation pH and type on these processes. In a cross-over study, two posaconazole suspensions (40 mg dispersed in 240 mL water at pH 1.6 and pH 7.1, respectively) were intragastrically administered; subsequently, gastric and duodenal fluids were aspirated. In parallel, blood samples were collected. Additionally, posaconazole was intragastrically administered as a solution (20 mg in 240 mL water, pH 1.6). When posaconazole was administered as an acidified suspension, supersaturated duodenal concentrations of posaconazole were observed for approximately 45 min. However, extensive intestinal precipitation was observed. Administration of the neutral suspension resulted in subsaturated concentrations with a mean duodenal AUC0-120 min and Cmax being approximately twofold lower than for the acidified suspension. The mean plasma AUC0-8 h of posaconazole was also twofold higher following administration of the acidified suspension. Similar to the acidified suspension, significant intestinal precipitation (up to 92%) was observed following intragastric administration of the posaconazole solution. This study demonstrated for the first time the gastrointestinal behavior of a weakly basic drug administered in different conditions, and its impact on systemic exposure.

show abstract

Designing a Dynamic Dissolution Method: A Review of Instrumental Options and Corresponding Physiology of Stomach and Small Intestine

Cited by 40 publications

References 102 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

Drug release from matrix tablets: physiological parameters and the effect of food

Supersaturation and Precipitation of Posaconazole Upon Entry in the Upper Small Intestine in Humans

Contact Info

Product

Resources

About