Gut instincts: Explorations in intestinal physiology and drug delivery

McConnell, Emma; Fadda, Hala M.; Basit, Abdul W.

doi:10.1016/j.ijpharm.2008.05.012

Cited by 406 publications

(258 citation statements)

References 191 publications

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“…Contents of the small intestine are buffered mainly by bicarbonate ions, which are secreted by the pancreas and intestinal epithelial cells. Other ions and luminal constituents, such as bile salts, proteins, carbohydrates, and other food components also contribute to the final buffer capacity and the pH (3)(4)(5)(6). However, as they play a minor role, the bicarbonate buffer is considered being the most biorelevant buffer system for the simulation of intestinal conditions (7,8).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it has been shown that bicarbonate buffers are more discriminative than compendial phosphate buffers and allow a better estimation of drug release from pH responsive formulations such as coated dosage forms intended to release the drug in the ileocecal region. It has also been demonstrated that bicarbonate buffers media enable a better prediction of in vivo disintegration times and drug release from products containing ionizable compounds (4,7,8,(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

et al. 2013

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Abstract. The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of carbon dioxide (CO 2 ) from the solution results in an uncontrolled increase of the pH. In order to maintain the pH on the desired level, either a CO 2 loss must be completely avoided or the escaped CO 2 has to be replaced by quantitative substitution, i.e. feeding the solution with the respective amount of gas, which re-acidifies the buffer after dissociation. The present work aimed at the development of a device enabling an automatic pH monitoring and regulation of hydrogen carbonate buffers during dissolution tests.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

et al. 2013

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“…Similarly, the dissolution behavior of mesalazine entericcoated tablet has shown that the use of bicarbonate buffer provides improved predictive power compared to compendial phosphate buffers (107). However, Boni et al (108) emphasized that the bicarbonate buffer has to be freshly prepared to produce reproducible dissolution profiles.…”

Section: Bicarbonate Buffermentioning

confidence: 99%

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

Bou‐Chacra

Melo

Morales

et al. 2017

AAPS J

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Abstract.The introduction of the biopharmaceutics drug classification system (Biopharmaceutics Classification System (BCS)), in 1995, provided a simple way to describe the biopharmaceutics behavior of a drug. Solubility and permeability are among the major parameters, which determine the fraction dose absorbed of a drug substance and consequently its chances to be bioavailable. The purpose of this review is to summarize the evolution of the media used for determining solubility and dissolution and how this can be used in modern drug development. Over the years, physiologically adapted media and buffers were introduced with the intention to better predict the in vivo solubility and dissolution of drug substances. Water, buffer solutions, compendial media, micellar solubilization media, and biorelevant media are reviewed. At this time point, there is no universal medium available which can be used to predict every drug substance's solubility or a drug product's in vivo dissolution behavior. However, there have been many improvements and additions made to media to optimize their in vivo predictability; for example, the current phosphate concentrations in buffers seem to be too high to correlate with the carbonate buffer concentrations in vivo. Biorelevant media were updated to correlate them better with the composition of human intestinal fluids. The BCS was introduced into regulatory sciences as a scientific risk management tool to waive bioequivalence studies under certain conditions. Today's different guidance documents define the dose-solubility ratio differently. As shown for amoxicillin, this can cause more confusion than certainty for globally operating companies. Harmonization of BCS guidelines is highly desirable.

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“…This cyclic contractility is called the migrating motility complex (MMC). The MMC in the fed state is replaced by regular, tonic contractions that propel food towards the antrum and mix it with gastric secretions [54,55]. The GI motility can thus affect or influence gastric-emptying rates, mixing patterns of solids and liquids in the stomach and intestine and intestinal transit times.…”

Section: Physiological Parametersmentioning

confidence: 99%

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

Nokhodchi

Asare-Addo

2014

Expert Opinion on Drug Delivery

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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.

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Gut instincts: Explorations in intestinal physiology and drug delivery

Cited by 406 publications

References 191 publications

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

An Automated System for Monitoring and Regulating the pH of Bicarbonate Buffers

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

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

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