Evidence map›Paper›PMID 42527804›Full record

ArticlePharmaceutical research2026

Development of an In Vitro Permeation Test Framework For Naloxone Hydrochloride Intranasal Spray: Establishing IVIVR for Bioequivalence Assessment.

Tasmin Ara Sultana, Manar Al-Ghabeish, Steven Chopski, Ross Walenga, Diaa Shakleya, Bryan Newman, Muhammad Ashraf, Ahmed Zidan

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Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Tasmin Ara SultanaDivision of Pharmaceutical Quality Research V, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Manar Al-GhabeishDivision of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Steven ChopskiDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Ross WalengaDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Diaa ShakleyaDivision of Pharmaceutical Quality Research V, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Bryan NewmanDivision of Therapeutic Performance I, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
Muhammad AshrafDivision of Pharmaceutical Quality Research V, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Ahmed ZidanDivision of Pharmaceutical Quality Research V, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA. ahmed.zidan@fda.hhs.gov.ORCID http://orcid.org/0000-0002-5830-4213

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIntranasal (IN) naloxone achieves rapid systemic exposure necessary for effective opioid overdose reversal; yet establishing bioequivalence (BE) for fast-acting drug-device combination products remains challenging due to the interplay of formulation attributes, device performance, and nasal physiology. This study developed an in vitro permeation test (IVPT) approach designed to quantitatively relate the nasal permeation behavior of naloxone to its clinical pharmacokinetic (PK) performance through an in vitro-in vivo relationship (IVIVR).

methodsNaloxone hydrochloride (Narcan®, 4 mg/0.1 mL) was deposited onto artificial membranes and EpiAirway™ mucociliary tissues using a controlled aerosol-deposition system (VITROCELL® Cloud Alpha 12). Naloxone permeation was assessed under sink conditions using a validated LC-MS/MS method. Cumulative permeation at 20 and 120 min (F₂₀ and F₁₂₀, respectively) was correlated with clinical maximum plasma concentration (C

resultsPermeation profiles differed by substrate, with the hydrophilic membranes showing higher dissolution rates and EpiAirway™ tissues demonstrating dose-proportional transport despite lower deposited mass. The tissue-based IVIVR models showed strong linearity (R2 > 0.98) and mean prediction errors within accepted limits (≤ 10%), while artificial membranes consistently overpredicted the systemic exposure. IVIVE analysis further supported close temporal agreement with clinical absorption patterns.

conclusionThese findings indicate that a tissue-based IVPT-IVIVR framework may provide a translational tool for relating in vitro permeation behavior to systemic exposure, supporting its utility in formulation development and BE risk assessment of rapidly acting IN naloxone products.

Indexed as

NaloxoneNarcotic AntagonistsAdministration, IntranasalAnimalsArea Under CurveHumansMembranes, ArtificialNasal MucosaNasal SpraysPermeabilityTandem Mass SpectrometryTherapeutic EquivalencyMembranes, ArtificialNaloxoneNarcotic AntagonistsNasal Spraysbioequivalencein vitro–in vivo extrapolationin vitro–in vivo relationshipin vitro permeation testnaloxone

Identifiers

PMID42527804

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.