Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

Pedersen, Pernille Barbre; Vilmann, Peter; Bar‐Shalom, Daniel; Baldursdóttir, Stefanía

doi:10.1016/j.ejpb.2013.05.007

Cited by 78 publications

(58 citation statements)

References 46 publications

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“…No pepsin was included and the pH was increased from the suggested 1.6 to 2.5. The latter was done to reflect recent findings regarding the pH of human gastric-fluid aspirates (Kalantzi et al, 2006;Pedersen et al, 2013) and to avoid unnecessary wear on the stainless-steel fiber-optic dip probes used for concentration determination.…”

Section: Dissolution Media Preparationmentioning

confidence: 99%

Concomitant intake of alcohol may increase the absorption of poorly soluble drugs

Fagerberg

Sjögren

Bergström

2015

European Journal of Pharmaceutical Sciences

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Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug reactions to occur.

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Section: Dissolution Media Preparationmentioning

confidence: 99%

Concomitant intake of alcohol may increase the absorption of poorly soluble drugs

Fagerberg

Sjögren

Bergström

2015

European Journal of Pharmaceutical Sciences

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“…The viscosity values presented in Table 2-3 were within the values reported for human gastric 41 aspirates (1.7 cP to 9.3 cP at 50 s -1 ) which are only slightly higher than that of water or SGF or FaSSGF (1.1 cP) (Pedersen et al, 2013). The viscosity of thickeners dispersed into 900 mL of the media (Table 2-4) were not remotely close to that typically used in dissolution tests for the fed stated (500 cP) based on approximate values calculated from extrapolation data in Radwan et al…”

Section: Discussionsupporting

confidence: 62%

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Torres¹,

Juliana²

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Medications are often crushed and mixed with foods or fluids to aid drug delivery for those who cannot or prefer not to swallow whole tablets or capsules. Dysphagic patients have the added problem of being unable to safely swallow fluids, so thickeners are added to ensure safe swallowing. These thickened fluids are then also used to deliver crushed medications in replacement of water. This thesis explores the influence of thickened water co-administration on drug release in gastric fluid, the effect of rheological properties of these agents and their contribution to describing the mechanism of release. The literature review (Chapter 1) examines oral dosage form administration, rheological properties of these agents as a means to ensure medication delivery and mechanisms of drug release. It is highlighted that thickened fluids have the potential to alter drug release but prediction of the effect of co-administration is not currently reported.Chapter 2 investigates the delivery of medications with thickened fluids as an indicator for potential compromise of drug bioavailability. In vitro dissolution in simulated gastric fluid is investigated for crushed atenolol immediate release tablets mixed with thickened fluids. Five commercial viscosityincreasing agents of varied polysaccharide composition are used at three thickness levels prescribed for dysphagic patients (levels 150, 400, 900). All types of thickening agents are non-Newtonian shear thinning fluids. The greatest thickness (level 900) significantly restricts dissolution, and products that are primarily based on xanthan gum also significantly delay dissolution at the intermediate thickness level (level 400). The interactions of the polysaccharide chains, particularly the rigid rod type conformation of xanthan gum, traps drug molecules within it resulting in impaired dissolution. Under the conditions of this experiment, the higher concentrations of thickening agents remain in large lumps rather than disintegrating into the media. Drug release is generally affected to a greater extent by high-viscosity fluids than low-viscosity fluids at 50 s -1 , but viscosity at this single shear rate of 50 s -1 is not a good indicator for effect on drug dissolution because viscosity changes with shear rate. The determination of other rheological parameters such as viscoelasticity and the effect of breaking up of the structures may be required.To investigate whether it is possible to improve drug release from thickened fluids, in Chapter 3 the effect of the state of aggregation of the active ingredient with thickened fluids is investigated.Paracetamol is the model drug because it is available in a range of formulations with the drug in solution (elixir, dissolved effervescent tablet) or dispersion (suspension). Xanthan gum, which causes the greatest restriction on dissolution (Chapter 2), is used at level 900 as the thickener.ii Crushed tablets with thickener are prepared using manual (i.e. the standard method in clinical practice) or mechanical mixing. The unthickene...

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“…Surface tension values range from 31 to 45 mN/m with a median value of 36.8 in the fasted gastric juice, whereas similar values of ~ 30 mN/m have been reported or observed in all GI compartments in the fed state [17,20,22,46]. Duodenal surface tension in the fasted state is reported to be in the same range as that in the gastric juice.…”

Section: Physiological Parametersmentioning

confidence: 59%

“…Reported values in the fasted for gastric osmolarity, duodenal fluids and the fluids in the jejunum have been reported to range between 119 and 221 mOsm with a median value of 202 mOsm, 137 and 224 mOsm with a median value of 197 mOsm and 200 and 300 mOsm with a median of 280 mOsm, respectively [12,18,20,22,23,26,28,45,46]. Values in the fed state for gastric osmolarity are to be 388 mOsm, with duodenal fluids osmolarity ranging from 276 and 416 mOsm [12,19,22,28,45].…”

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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Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

Cited by 78 publications

References 46 publications

Concomitant intake of alcohol may increase the absorption of poorly soluble drugs

Concomitant intake of alcohol may increase the absorption of poorly soluble drugs

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

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

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