Evidence map›Paper›PMID 42711604›Full record

ArticleThe AAPS journal2026

Investigating the Impact of Food Induced Fluid Viscosity on Disintegration and Dissolution of Immediate Release Midodrine HCl Tablet.

Fathima T Doole, Ranganath Wahalathantrige Don, Ishwor Poudel, Timothy Lex, Yi-Hsien Cheng, Fang Wu, Wei-Jhe Sun, Lei Zhang, Peter Langguth, Wenlei Jiang and 1 more

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Article in The AAPS journal, 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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0cells of the map it votes in
0citing papers 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

11 authors.

Fathima T DooleOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, Missouri, 63110, USA.ORCID http://orcid.org/0000-0001-8270-5175
Ranganath Wahalathantrige DonOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, Missouri, 63110, USA.ORCID http://orcid.org/0000-0002-8453-8638
Ishwor PoudelOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, Missouri, 63110, USA.ORCID http://orcid.org/0000-0002-1543-6785
Timothy LexOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, Missouri, 63110, USA.ORCID http://orcid.org/0000-0002-7454-8322
Yi-Hsien ChengOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.ORCID http://orcid.org/0000-0002-4314-9732
Fang WuOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.ORCID http://orcid.org/0009-0009-1485-8386
Wei-Jhe SunOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.ORCID http://orcid.org/0009-0005-3306-3096
Lei ZhangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.ORCID http://orcid.org/0000-0002-0639-3162
Peter LangguthDepartment of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.ORCID http://orcid.org/0000-0003-3758-7581
Wenlei JiangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA. Wenlei.jiang@fda.hhs.gov.ORCID http://orcid.org/0009-0009-3876-638X
Zongming GaoOffice of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, Missouri, 63110, USA. Zongming.gao@fda.hhs.gov.ORCID http://orcid.org/0009-0002-2038-7401

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The prediction of bioavailability (BA) and bioequivalence (BE) for immediate-release (IR) solid oral dosage forms is critical during development and post-approval phases of drug products. ICH M13A provides the option of using in vitro tests, such as disintegration and dissolution in biorelevant media, pilot studies, and modeling to justify not conducting in vivo fed BE studies. The gastrointestinal (GI) tract environment changes significantly after food intake, including variations in pH, enzyme activity, and fluid viscosity that influence drug dissolution and absorption. Existing biorelevant dissolution media (FeSSIF, FeSSGF etc.) simulate human GI fluid composition but do not account for food-induced viscosity changes. This study explored impacts of food-induced fluid viscosity (pH 1.2 buffer containing hydroxypropyl methylcellulose (HPMC)) on disintegration and dissolution profiles of midodrine HCl tablets. Using USP Apparatus II and disintegration testing, we evaluated dissolution and disintegration of five approved generic midodrine HCl tablets with demonstrated BE. High-viscosity media significantly delayed tablet disintegration and drug dissolution compared to low-viscosity fasting conditions. We modified dissolution methods to closely simulate fed state GI conditions by varying agitation speed, prolonging dissolution time, adding medium stagewise to simulate dilution of gastric fluid, and adding water to mimic co-administered drinks. Results showed increased dissolution with higher agitation speeds and continued dissolution in viscous media over extended time. Stagewise dissolution in medium with reduced viscosity to mimic gastric secretion did not accelerate drug release compared to viscous media. In contrast, co-administered water enabled tablet swelling and disintegration, leading to complete drug release within 15 min, which is more consistent with the in vivo PK data under fed conditions. These findings may help refine in vitro dissolution conditions to better mimic fed-state.

Indexed as

Food-Drug InteractionsBiological AvailabilityBulk DrugsDrug LiberationHumansHydrogen-Ion ConcentrationHypromellose DerivativesSolubilityTabletsTherapeutic EquivalencyViscosityBulk DrugsHypromellose DerivativesTabletsBEDisintegrationFast and fed conditionICHin vitro dissolution testing

Identifiers

PMID42711604

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Registered trials

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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.