The dynamic gastric environment and its impact on drug and formulation behaviour

Abeele, Jens Van Den; Rubbens, Jari; Brouwers, Joachim; Augustijns, Patrick

doi:10.1016/j.ejps.2016.08.060

Cited by 81 publications

(65 citation statements)

References 352 publications

(551 reference statements)

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“…The relatively large between‐subject variability in fasted state could be due to the differences in stomach pH, STT, and T precip among individuals …”

Section: Resultsmentioning

confidence: 99%

Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics

Lu¹,

Fraczkiewicz

Salphati

et al. 2017

CPT Pharmacom & Syst Pharma

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Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan‐inhibitor of phosphatidylinositol 3‐kinases for oncology indications. To investigate the significance of high‐fat food and gastric pH on pictilisib pharmacokinetics (PK) and enable label recommendations, a dedicated clinical study was conducted in healthy volunteers, whereby both top‐down (population PK, PopPK) and bottom‐up (physiologically based PK, PBPK) approaches were applied to enhance confidence of recommendation and facilitate the clinical development through scenario simulations. The PopPK model identified food (for absorption rate constant (Ka)) and proton pump inhibitors (PPI, for relative bioavailability (Frel) and Ka) as significant covariates. Food and PPI also impacted the variability of Frel. The PBPK model accounted for the supersaturation tendency of pictilisib, and gastric emptying physiology successfully predicted the food and PPI effect on pictilisib absorption. Our research highlights the importance of applying both quantitative approaches to address critical drug development questions.

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“…The relatively large between‐subject variability in fasted state could be due to the differences in stomach pH, STT, and T precip among individuals …”

Section: Resultsmentioning

confidence: 99%

Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics

Lu¹,

Fraczkiewicz

Salphati

et al. 2017

CPT Pharmacom & Syst Pharma

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“…Many factors can affect floating strength of formulations including gastric emptying time and pH of the stomach. Buoyancy kinetics of granules could be significantly altered in response to gastric churning movements and can affect the desired performance of the drug delivery system (Van Den Abeele et al, 2017). Floating strength should be high enough to be robust to these potential issues and allow for consistent performance of the delivery system.…”

Section: Floating Strength Of the Granulesmentioning

confidence: 99%

Preparation and evaluation of cefuroxime axetil gastro-retentive floating drug delivery system via hot melt extrusion technology

Lalge

Thipsay

Shankar

et al. 2019

International Journal of Pharmaceutics

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Cefuroxime Axetil (CA) is a poorly soluble, broad spectrum antibiotic which undergoes enzymatic degradation in gastrointestinal tract. The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery systems containing CA using hot-melt extrusion (HME) to improve absorption. Selected formulations of CA and lipids were extruded using a twin screw hotmelt extruder. Milled extrudates were characterized for dissolution, floating strength, and micromeritic properties. Solid-state characterization was performed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and hot-stage microscopy. In vitro characterization demonstrated that the *

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“…However, the conventional oral method of administration that is often employed for small molecules presents a difficult barrier for biological compounds. The intestine–liver axis first-pass metabolism can significantly influence drug or nutraceutical metabolism [7]. Additional gastrointestinal limitations also can significantly influence the metabolism and efficacy of a compound.…”

Section: Introductionmentioning

confidence: 99%

“…Additional gastrointestinal limitations also can significantly influence the metabolism and efficacy of a compound. Such limitations include reduced absorption due to the large molecular sizes of biological compounds, a high degree of enzymatic degradation (i.e., by proteolytic enzymes present in the intestinal epithelia and lumen), or a high degree of chemical instability due to the luminal low-pH environment [7,8]. …”

Section: Introductionmentioning

confidence: 99%

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum

Vitetta

Zhou²,

Manuel³

et al. 2018

JFB

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The administration of biological compounds that optimize health benefits is an ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological compounds have been administered via many different routes in order to produce a systemic pharmacological effect. The article summarizes the findings from an Australian comparative study in adults administered vitamin B12 through different oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily partook in a comparative clinical study of five different vitamin B12 formulations across a six-month period, completing 474 person-hours of cumulative contribution, that was equivalent to an n = 60 participation. A nanoparticle delivered vitamin B12 through a NanoCelle platform was observed to be significantly (p < 0.05) better absorbed than all other dose equivalent platforms (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the study period. The nanoparticle platform delivered vitamin B12 demonstrated an enhanced and significant absorption profile as exemplified by rapid systemic detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa with no reports of any adverse events of toxicity. The nanoparticle formulation of methylcobalamin (1000 µg/dose in 0.3 mL volume) showed bioequivalence only with a chewable-dissolvable tablet that administered a five times higher dose of methylcobalamin (5000 µg) per tablet. This study has demonstrated that an active metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug delivery method that can better access the circulatory system.

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The dynamic gastric environment and its impact on drug and formulation behaviour

Cited by 81 publications

References 352 publications

Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics

Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics

Preparation and evaluation of cefuroxime axetil gastro-retentive floating drug delivery system via hot melt extrusion technology

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum

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