The Organization of the Gut and the Oral Absorption of Drugs: Anatomical, Biological and Physiological Considerations in Oral Formulation Development

Wilson, Clive G.

doi:10.1007/978-1-4614-1004-1_2

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…This could be attributed to an oxidative degradation in the GI tract, low concentration in plasma/urine or quick absorption (<1 h) and tissue distribution, or metabolism into ferulic acid [ 32 ]. Phenolic compounds identified in plasma showed a T max of 1–4 h after mango consumption, suggesting that the absorption of these phenolics occurred in the small intestine [ 33 ]. Even though some phenolic compounds such as gallic, chlorogenic, caffeic, and p -coumaric acids can be absorbed in the stomach via monocarboxylic acid transporters (MCTs) within 5 min after gastric administration [ 34 ], the small intestine is known to be the major site for the absorption of phenolic acids.…”

Section: Discussionmentioning

confidence: 99%

Processing ‘Ataulfo’ Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds

et al. 2017

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The health-promoting effects of phenolic compounds depend on their bioaccessibility from the food matrix and their consequent bioavailability. We carried out a randomized crossover pilot clinical trial to evaluate the matrix effect (raw flesh and juice) of ‘Ataulfo’ mango on the bioavailability of its phenolic compounds. Twelve healthy male subjects consumed a dose of mango flesh or juice. Blood was collected for six hours after consumption, and urine for 24 h. Plasma and urine phenolics were analyzed by electrochemical detection coupled to high performance liquid chromatography (HPLC-ECD). Five compounds were identified and quantified in plasma. Six phenolic compounds, plus a microbial metabolite (pyrogallol) were quantified in urine, suggesting colonic metabolism. The maximum plasma concentration (Cmax) occurred 2–4 h after consumption; excretion rates were maximum at 8–24 h. Mango flesh contributed to greater protocatechuic acid absorption (49%), mango juice contributed to higher chlorogenic acid absorption (62%). Our data suggests that the bioavailability and antioxidant capacity of mango phenolics is preserved, and may be increased when the flesh is processed into juice.

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Section: Discussionmentioning

confidence: 99%

Processing ‘Ataulfo’ Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds

et al. 2017

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“…At lower values of k m and k i ′ representing higher resistances, the surface pH was predicted to increase and nearly plateau at 6.1 (Figure ). At this higher pH (6.0) that was not accessible experimentally, in all cases, the desupersaturation was predicted to have a duration of not less than 3 h. Drug transit through the small intestine (a major site of absorption) in healthy individuals varies between 3 and 4 h . Maintenance of supersaturation in vivo such as that predicted by this model can result in higher bioavailability .…”

Section: Resultsmentioning

confidence: 81%

Mechanisms for the Slowing of Desupersaturation of a Weak Acid at Elevated pH

Manchanda

Bogner

2020

Mol. Pharmaceutics

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Supersaturating drug delivery systems are used to achieve higher oral bioavailability for poorly soluble drugs. However, supersaturated solutions often decline to lower concentrations by precipitation and crystallization. The purpose of the current research is to provide a mechanistic understanding of drug crystallization as a function of pH, using indomethacin (IMC, pK a 4.18) as a model compound. Desupersaturation kinetics to the γ-form of IMC was measured at pH 2.0, 3.0, 4.0, and 4.5 from an initial degree of supersaturation of 2.5−6. At equivalent levels of supersaturation, crystal growth rates decreased with an increase in solution pH. Two mechanisms for this phenomenon, reactive diffusion (resulting in a higher surface pH as compared to bulk pH) and inhibition of crystallization by structurally similar ionized IMC at higher pH, were explored. Non-steady-state models for reactive diffusion showed that the surface pH was only 0.01 units above that of the bulk solution pH. Mass transport models for reactive diffusion during crystallization could not explain the decrease in desupersaturation kinetics at higher pH. However, zeta potentials as high as −70 mV suggested that IMC − is adsorbed on the surface of the particles. A mathematical model for inhibition of crystal growth by IMC − accounted for the pH effect suggesting that ionized IMC acts as an effective crystallization inhibitor of IMC.

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“…Each formulation was evaluated in acidic (pH = 1.2) and neutral (pH = 6.8) media for 2 h, which matches the mean residence time of tablets in the stomach and duodenum. 26 The total medium volume was 500 mL, and the flow rate was set at 10 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Effect of Excipients on Salt Disproportionation during Dissolution: A Novel Application of In Situ Raman Imaging

et al. 2021

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We have employed a bespoke setup combining confocal Raman microscopy and an ultraviolet–visible (UV–Vis) spectroscopy flow cell to investigate the effect of excipients on the disproportionation kinetics of Pioglitazone HCl (PioHCl) in tablets during dissolution. Three binary formulations of PioHCl, containing citric acid monohydrate (CA), lactose monohydrate (LM), or magnesium stearate (MgSt), respectively, were used as models to study the influence of excipients’ physicochemical properties on the rate of salt disproportionation kinetics and dissolution performance in different aqueous pH environments. It was found that formulation excipients can induce or prevent salt disproportionation by modulating the microenvironmental pH regardless of the pH of the dissolution media. Incorporating CA in PioHCl tablets preserves the salt form and enhances the dissolution performance of the salt in the acidic medium (pH = 1.2). In contrast, LM and MgSt had a detrimental effect on in vitro drug performance by inducing salt disproportionation in the tablet during dissolution in the same acidic medium. Dissolution in the neutral medium (pH = 6.8) showed rapid formation of the free base upon contact with the dissolution medium. The Raman maps of the cross-sectioned tablets revealed the formation of a shell consisting of the free base around the edge of the tablet. This shell decreased the rate of penetration of the dissolution medium into the tablet, which had significant implications on the release of the API into the surrounding solution, as shown by the UV–vis absorption spectroscopy drug release data. Our findings highlight the utility of the Raman/UV–vis flow cell analytical platform as an advanced analytical technique to investigate the effect of excipients and dissolution media on salt disproportionation in real time. This methodology will be used to enhance our understanding of salt stability studies that may pave the way for more stable multicomponent formulations.

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The Organization of the Gut and the Oral Absorption of Drugs: Anatomical, Biological and Physiological Considerations in Oral Formulation Development

Cited by 7 publications

References 34 publications

Processing ‘Ataulfo’ Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds

Processing ‘Ataulfo’ Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds

Mechanisms for the Slowing of Desupersaturation of a Weak Acid at Elevated pH

Effect of Excipients on Salt Disproportionation during Dissolution: A Novel Application of In Situ Raman Imaging

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