In silico model of drug permeability across sublingual mucosa

Goswami, Tarun; Kokate, Amit; Jasti, Bhaskara; Li, Xiaoling

doi:10.1016/j.archoralbio.2012.09.020

Cited by 22 publications

(8 citation statements)

References 29 publications

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“…1). Moreover, these results are in good agreement with values found in the literature for sublingual caffeine permeability (Papp = (1 520 ± 310)×10 -8 cm/s; Goswami et al, 2013). Fig.…”

Section: Permeation Experimentssupporting

confidence: 91%

In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats

Berka

Stránská²,

Semecký

et al. 2019

Preprint

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Graphical abstractKeywords sublingual drug administration; porcine sublingual membrane; in vitro permeability; caffeine; dextran; bovine serum albumin; nanofiber drug carrier Abstract Sublingual drug delivery allows systemic delivery of drug without difficulties connected with the gastrointestinal pathway. We developed a new simple protocol for easy-to-use processing and storage of porcine sublingual mucosal membrane for in vitro studies using "flash freezing" in liquid nitrogen. All the dextrans used as mucosal membrane integrity and permeability markers permeated only slowly through sublingual mucosa illustrating usability both the "fresh" and "flash frozen" sublingual membranes whereas conventional cold storage "frozen" membranes have shown significantly higher permeabilities for macromolecules due to the sustained damage. The permeability values were too low to expect dextrans to be potential carriers at this context. To test albumin as a drug carrier we compared FITC-albumin permeation from solutions vs. nanofiber mats donors. To increase the amounts and prolong the transport , we manufactured nanofiber mats loaded with fluorescently marked albumin using well-scalable electrospinning technology. Nanofiber mats have allowed albumin passage through the sublingual membrane in similar amounts as from the pure artificial saliva solution.Since salivary washout strictly limits the duration of liquid dosages, nanofiber mats may thus permit prolonged sublingual administration.

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“…1). Moreover, these results are in good agreement with values found in the literature for sublingual caffeine permeability (Papp = (1 520 ± 310)×10 -8 cm/s; Goswami et al, 2013). Fig.…”

Section: Permeation Experimentssupporting

confidence: 91%

In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats

Berka

Stránská²,

Semecký

et al. 2019

Preprint

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“…The physicochemical properties generally preferred for common routes of delivery have been reviewed (Mathias and Hussain 2010) and key parameters are summarized in Table 2.9. Further details may be found in recent reviews for transdermal (Neely et al 2009;Paudel et al 2010;Watkinson 2013), intranasal (Chapman et al 2013), and sublingual/buccal delivery Goswami et al 2013;Lam et al 2013). Strict limitations around human efficacy dose (Table 2.10) for nonoral routes of administration are due primarily to permeation limitations or dose volume constraints at these sites.…”

Section: Formulation Considerations For Alternate Drug Deliverymentioning

confidence: 99%

Discovering and Developing Molecules with Optimal Drug-Like Properties

Templeton¹,

Byrn²,

Haskell³

et al. 2015

AAPS Advances in the Pharmaceutical Sciences Series

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“…There is increasing interest in the early feasibility assessment of IO delivery of drug molecules based on their physicochemical properties [13]. Clearly, a simplified first-order absorption model of the oral cavity is not adequate to integrate the complexity of IO physiology, physicochemical properties, formulation effects, and dosing scenarios.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

Xia

Yang

Zhou

et al. 2015

AAPS J

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Abstract. Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C max , T max , and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F a_IO ). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R 2 >0.9). The predicted deviations (%) for C max , AUC 0-inf , AUC 0-20 min , and T max were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F a_IO was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f ut ) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD pH=7.4 ). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations.KEY WORDS: diffusivity; intraoral delivery; oral cavity compartmental absorption and transit (OCCAT™) model; unbound fraction in epithelium tissue; zolpidem.

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In silico model of drug permeability across sublingual mucosa

Cited by 22 publications

References 29 publications

In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats

In vitro testing of flash-frozen sublingual membranes for storage and reproducible permeability studies of macromolecular drugs from solution or nanofiber mats

Discovering and Developing Molecules with Optimal Drug-Like Properties

Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

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