pH-dependent ileocolonic drug delivery, part I: in vitro and clinical evaluation of novel systems

Broesder, Annemarie; Woerdenbag, Herman J.; Prins, Grietje H.; Nguyen, Duong Nhat; Frijlink, Henderik W.; Hinrichs, Wouter L. J.

doi:10.1016/j.drudis.2020.06.011

Cited by 9 publications

(10 citation statements)

References 119 publications

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“…Therefore, a smaller colonic free fluid volume in the paediatric colon compared with an adult cohort is expected. However, not all colonic parameters change with maturation, e.g., the pH of the paediatric colon children aged 8–14 years is reported to be comparable to adult values [ 56 , 57 ]. Similarly, no significant difference was detected in the fluid volumes between the four different paediatric age groups, (consistent with the existing data on small intestinal fluid volumes) in children [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

et al. 2021

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Previous studies have used magnetic resonance imaging (MRI) to quantify the fluid in the stomach and small intestine of children, and the stomach, small intestine and colon of adults. This is the first study to quantify fluid volumes and distribution using MRI in the paediatric colon. MRI datasets from 28 fasted (aged 0–15 years) and 18 fluid-fed (aged 10–16 years) paediatric participants were acquired during routine clinical care. A series of 2D- and 3D-based software protocols were used to measure colonic fluid volume and localisation. The paediatric colon contained a mean volume of 22.5 mL ± 41.3 mL fluid, (range 0–167.5 mL, median volume 0.80 mL) in 15.5 ± 17.5 discreet fluid pockets (median 12). The proportion of the fluid pockets larger than 1 mL was 9.6%, which contributed to 94.5% of the total fluid volume observed. No correlation was detected between all-ages and colonic fluid volume, nor was a difference in colonic fluid volumes observed based on sex, fed state or age group based on ICH-classifications. This study quantified fluid volumes within the paediatric colon, and these data will aid and accelerate the development of biorelevant tools to progress paediatric drug development for colon-targeting formulations.

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Section: Discussionmentioning

confidence: 99%

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

et al. 2021

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“…The ColoPulse coating is a pH-dependent coating that can be used to obtain ileocolonic drug delivery with a pulsatile drug release profile [1]. The pH in the lumen of the gastrointestinal tract remains below pH 7.0 until the terminal ileum is reached where it exceeds this pH [2]. The ColoPulse coating is based on Eudragit S100, a pH-sensitive polymer, which dissolves at pH values above 7.0 [3].…”

Section: Introductionmentioning

confidence: 99%

Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery

et al. 2021

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The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

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“…To evaluate the in vitro dissolution profiles of the manufactured formula, different prototypes were tested by means of state-of-the-art dissolution assays, mimicking gastrointestinal conditions 32 , 33 . Development and in vitro testing of the caffeine pulsatile-release formulation and placebos was conducted at Elixir Pharmaceutical Research and Development Corporation in Ankara.…”

Section: Methodsmentioning

confidence: 99%

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening

Dornbierer

Yerlikaya

Wespi

et al. 2021

Sci Rep

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Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360.

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pH-dependent ileocolonic drug delivery, part I: in vitro and clinical evaluation of novel systems

Cited by 9 publications

References 119 publications

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

Quantification of Fluid Volume and Distribution in the Paediatric Colon via Magnetic Resonance Imaging

Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening

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