Early pharmaceutical profiling to predict oral drug absorption: Current status and unmet needs

Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup; Andersson, Sara; Artursson, Per; Beato, Stefania; Borde, Anders; Box, Karl; Brewster, Marcus E.; Dressman, Jennifer B.; Feng, Kung I.; Halbert, Gavin; Kostewicz, Edmund; McAllister, Mark; Muenster, Uwe; Thinnes, Julian; Taylor, Robert W.; Müllertz, Anette

doi:10.1016/j.ejps.2013.10.015

Cited by 229 publications

(206 citation statements)

References 317 publications

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“…Buffer capacity values ranging from 2 to 13 mM/L/pH have also been reported for the small intestine in the fasted state [26,38]. The buffer capacity is higher in the fed state as compared to the fasted state for gastric (19.5 mM/pH), duodenal (24 --30 mM/pH) and jejunal fluids (13.9 mM/pH) [12,19,22,37,38,45].…”

Section: Physiological Parametersmentioning

confidence: 79%

“…The methods for the aspiration of gastric or intestinal fluids and characterising them are vast and well documented in literature. This is not covered in this review and interested readers are directed to Bergstrom et al [12] and all the references therein.…”

Section: Physiological Parametersmentioning

confidence: 99%

“…Typical median values are around 5 during the later postprandial state for the small intestine [33,34]. Pre-treatment of a meal in the stomach means that the pH of the intestinal fluids is not as affected to the same extent as gastric fluids as such fed state fluid in the duodenum have been reported to be between 5.4 and 6.5 [12,19,21,22,28,[35][36][37].…”

Section: Physiological Parametersmentioning

confidence: 99%

“…Another explanation is that, the absorption of SCFA is linked to the accumulation of bicarbonate in the lumen, which is explained by the presence of an acetate--bicarbonate exchange at the surface of the mucosal cells [40,[42][43][44]. Three studies determined the buffer capacity of gastric fluid to range between 13.3 and 19.0 mM/DpH with a median value of 14.3 [12,20,22,26]. Buffer capacity values ranging from 2 to 13 mM/L/pH have also been reported for the small intestine in the fasted state [26,38].…”

Section: Physiological Parametersmentioning

confidence: 99%

“…The GI fluid is a complex and dynamic mixture of components from a number of sources within the GI tract and its composition can have a huge impact on the solubility and dissolution of poorly soluble APIs [12]. Gastric fluid is a com-position of saliva, gastric secretions, dietary food and liquid and secretions from the liver [4].…”

Section: Physiological Parametersmentioning

confidence: 99%

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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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Section: Physiological Parametersmentioning

confidence: 79%

Section: Physiological Parametersmentioning

confidence: 99%

Section: Physiological Parametersmentioning

confidence: 99%

Section: Physiological Parametersmentioning

confidence: 99%

Section: Physiological Parametersmentioning

confidence: 99%

See 3 more Smart Citations

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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Preclinical and Clinical Studies

Brewster¹,

Verreck²,

Bevernage³

et al. 2015

Pharmaceutical Sciences Encyclopedia

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Contemporary drug pipelines are increasingly populated with difficult‐to‐formulate drug substances. Amorphous solid dispersions can increase drug dissolution rate by reducing the effective drug particle size through its dispersion in the matrix. Based on the theorized way of working of amorphous solid dispersions, one of the most important design elements is their ability to dissolve and supersaturate. This is initially assessed in vitro through the use of dissolution protocols especially set up for that purpose. A number of in vivo assessments of the potential utility of amorphous solid dispersions have been completed using various animal models. Clinical assessments to investigate itraconazole supersaturation (indirectly) have also been completed. Itraconazole is a widely studied compound in this context with numerous in vitro , in vivo , and clinical evaluations completed. Useful preclinical and clinical models for assessing solid dispersion fitness will contribute to the drug development process.

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Lead Identification/Optimization

Wong

McAllister

2017

Oral Formulation Roadmap From Early Drug Discovery to Development

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Early pharmaceutical profiling to predict oral drug absorption: Current status and unmet needs

Cited by 229 publications

References 317 publications

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

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

Preclinical and Clinical Studies

Lead Identification/Optimization

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