---
title: "Ultrasonic detection of irreversible moisture effects on tablet microstructure and micro-viscoelas"
id: "pubmed-42567374"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42567374"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42567374/"
doi: "10.1016/j.ijpharm.2026.127277"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Ultrasonic detection of irreversible moisture effects on tablet microstructure and micro-viscoelas
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42567374
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42567374/)
- **DOI:** [10.1016/j.ijpharm.2026.127277](https://doi.org/10.1016%2Fj.ijpharm.2026.127277)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Moisture exposure by uniform vapor diffusion (no direct liquid contact) increased tablet mass by about **8.3 ± 0.77%**, demonstrating uptake without surface wetting. - A controlled dry-down following moisture exposure allowed serial ultrasonic acquisition using a custom pitch‑catch rig with paired pressure transducers. - Waveforms were analyzed in the temporal, spectral, and wave‑dispersion domains to extract both bulk- and microstructure-sensitive metrics. - Geometric recovery after drying was minimal: diameter, thickness, and mass density increased by approximately **0.97 ± 0.25%**, **1.83 ± 0.13%**, and **3.69 ± 0.49%**, respectively, relative to the initial dry state. - In contrast, substantial irreversible reductions were measured in ultrasonic-derived mechanical metrics: pressure wave speed (~**28.87%** reduction), group velocity (~**13.20%** reduction), and apparent modulus of elasticity (~**47.34%** reduction). - Residual stress assessment showed equivalent axial residual stress remained roughly **3–4 times** higher than equivalent radial residual stress after drying, indicating anisotropic, non-uniform recovery. - Findings indicate that **ultrasonic characterization** is a sensitive, non-destructive method to detect irreversible moisture-induced microstructural and micro-viscoelastic changes that are not apparent from gross geometric measurements. - The study frames ultrasonic assessment as a potential **Process Analytical Technology (PAT)** and quality-assurance tool relevant to **Continuous Manufacturing (CM)**, Critical Quality Attributes (CQA), Quality by Design (QbD), and real-time release testing (RTRT).
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 7. # Ultrasonic evaluation of permanent moisture impact on microstructural and micro-viscoelastic properties of pharmaceutical tablets: a proof of concept study [S H M Muntasir Rahi](https://pubmed.ncbi.nlm.nih.gov/?term=Muntasir+Rahi+SHM&cauthor_id=42567374)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-1 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: rahi@clarkson.edu."), [Ahmad Rasheeq Faiyaz](https://pubmed.ncbi.nlm.nih.gov/?term=Faiyaz+AR&cauthor_id=42567374)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-2 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: faiyaza@clarkson.edu."), [Tipu Sultan](https://pubmed.ncbi.nlm.nih.gov/?term=Sultan+T&cauthor_id=42567374)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-3 "Weill Cornell Medicine, Department of Radiology, New York, NY 10022, USA. Electronic address: tis4016@med.cornell.edu."), [Vivek S Dave](https://pubmed.ncbi.nlm.nih.gov/?term=Dave+VS&cauthor_id=42567374)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-4 "St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: vdave@sjf.edu."), [Ankit Rochani](https://pubmed.ncbi.nlm.nih.gov/?term=Rochani+A&cauthor_id=42567374)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-5 "St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: arochani@sjfc.edu."), [Cetin Cetinkaya](https://pubmed.ncbi.nlm.nih.gov/?term=Cetinkaya+C&cauthor_id=42567374)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#full-view-affiliation-6 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: ccetinka@clarkson.edu.") Affiliations Expand ### Affiliations * 1 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: rahi@clarkson.edu. * 2 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: faiyaza@clarkson.edu. * 3 Weill Cornell Medicine, Department of Radiology, New York, NY 10022, USA. Electronic address: tis4016@med.cornell.edu. * 4 St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: vdave@sjf.edu. * 5 St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: arochani@sjfc.edu. * 6 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: ccetinka@clarkson.edu. * PMID: **42567374** * DOI: [ 10.1016/j.ijpharm.2026.127277 ](https://doi.org/10.1016/j.ijpharm.2026.127277) Item in Clipboard # Ultrasonic evaluation of permanent moisture impact on microstructural and micro-viscoelastic properties of pharmaceutical tablets: a proof of concept study S H M Muntasir Rahi et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42567374/) . 2026 Sep 5:702:127277. doi: 10.1016/j.ijpharm.2026.127277. Epub 2026 Aug 7. ### Authors [S H M Muntasir Rahi](https://pubmed.ncbi.nlm.nih.gov/?term=Muntasir+Rahi+SHM&cauthor_id=42567374)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-1 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: rahi@clarkson.edu."), [Ahmad Rasheeq Faiyaz](https://pubmed.ncbi.nlm.nih.gov/?term=Faiyaz+AR&cauthor_id=42567374)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-2 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: faiyaza@clarkson.edu."), [Tipu Sultan](https://pubmed.ncbi.nlm.nih.gov/?term=Sultan+T&cauthor_id=42567374)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-3 "Weill Cornell Medicine, Department of Radiology, New York, NY 10022, USA. Electronic address: tis4016@med.cornell.edu."), [Vivek S Dave](https://pubmed.ncbi.nlm.nih.gov/?term=Dave+VS&cauthor_id=42567374)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-4 "St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: vdave@sjf.edu."), [Ankit Rochani](https://pubmed.ncbi.nlm.nih.gov/?term=Rochani+A&cauthor_id=42567374)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-5 "St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: arochani@sjfc.edu."), [Cetin Cetinkaya](https://pubmed.ncbi.nlm.nih.gov/?term=Cetinkaya+C&cauthor_id=42567374)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42567374/#short-view-affiliation-6 "Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: ccetinka@clarkson.edu.") ### Affiliations * 1 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: rahi@clarkson.edu. * 2 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: faiyaza@clarkson.edu. * 3 Weill Cornell Medicine, Department of Radiology, New York, NY 10022, USA. Electronic address: tis4016@med.cornell.edu. * 4 St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: vdave@sjf.edu. * 5 St. John Fisher University, Wegmans School of Pharmacy, Rochester, NY 14618, USA. Electronic address: arochani@sjfc.edu. * 6 Photo-Acoustics Research Laboratory, Clarkson University, Department of Mechanical and Aerospace Engineering, Potsdam, NY 13699-5725, USA. Electronic address: ccetinka@clarkson.edu. * PMID: **42567374** * DOI: [ 10.1016/j.ijpharm.2026.127277 ](https://doi.org/10.1016/j.ijpharm.2026.127277) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Moisture exposure can significantly affect the critical quality attributes of pharmaceutical tablets by altering their internal microstructure and micro-viscoelastic properties. In compressed granular materials, moisture-induced changes in chemical state, interparticle bonding, porosity, and residual stress distribution can alter both mechanical integrity and performance-related attributes. In this study, irreversible moisture-induced changes in tablet bulk, microstructural, and micro-viscoelastic properties were investigated and quantified using ultrasonics. As a result of uniform vapor diffusion into the samples (without direct liquid contact), moisture exposure increased tablet mass by approximately 8.3 ± 0.77%. Subsequently, the samples underwent a controlled dry-down phase during which ultrasonic waveforms were acquired using a custom-made rig in pitch-catch mode with paired pressure transducers. Waveforms acquired throughout the moisture cycle were analyzed in the temporal, spectral, and wave-dispersion domains to extract bulk- and microstructure-sensitive response metrics. It was observed that moisture exposure followed by controlled dry-down resulted in only minor residual geometric changes relative to the initial dry state, with diameter, thickness, and mass density showing average increases of approximately 0.97 ± 0.25%, 1.83 ± 0.13%, and 3.69 ± 0.49%, respectively. By contrast, substantial irreversible reductions were observed in pressure wave speed, group velocity, and apparent modulus of elasticity, by approximately 28.87%, 13.20%, and 47.34%, respectively. Equivalent axial residual stress remained approximately 3-4 times higher than equivalent radial residual stress after drying, indicating non-uniform recovery of deformation across directions. Overall, the findings demonstrate that the ultrasonic approach offers a sensitive, non-destructive means of detecting irreversible moisture-induced changes in tablet microstructure that are not captured by observable geometric recovery, highlighting its potential for quality assessment and monitoring applications. **Keywords:** Continuous manufacturing (CM); Critical quality attributes (CQA); Granular composite microstructure; Micro-viscoelastic properties; Moisture exposure; Non-destructive evaluation; Process analytical technology (PAT); Quality by design (QbD); Real-time release testing (RTRT); Residual stresses; Ultrasonic characterization; Wave dispersion analysis. Copyright © 2026. Published by Elsevier B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Microstructure-centric ultrasonic evaluation of granular composite oral solid dosage tablets. ](https://pubmed.ncbi.nlm.nih.gov/42442516/) Sultan T, Dave VS, Stephens J, Rochani A, Cetinkaya C.Sultan T, et al.Int J Pharm. 2026 Aug 10;701:127185. doi: 10.1016/j.ijpharm.2026.127185. Epub 2026 Jul 13.Int J Pharm. 2026.PMID: 42442516 * [ Machine learning framework for extracting micro-viscoelastic and micro-structural properties of compressed oral solid dosage forms. ](https://pubmed.ncbi.nlm.nih.gov/37797783/) Sultan T, Hasan Rozin E, Paul S, Tseng YC, Cetinkaya C.Sultan T, et al.Int J Pharm. 2023 Nov 5;646:123477. doi: 10.1016/j.ijpharm.2023.123477. Epub 2023 Oct 4.Int J Pharm. 2023.PMID: 37797783 * [ A review of the state-of-the-art: progress in ultrasonic and acoustic techniques for quality assessment in the development and manufacturing of oral solid dosage forms - Part I: theoretical foundations and principles. ](https://pubmed.ncbi.nlm.nih.gov/41297864/) Çetinkaya Ç, Bazzocchi M, Dave VS, Halkude B, Hussain AS, Prasad Vallabha CK, Razavi SM, Stephens J, Steiner R, Sultan T, Sun CK, Tantuccio AS, Tajarobi P, Ündey C, Wikström H, Xu X.Çetinkaya Ç, et al.Int J Pharm. 2026 Jan 5;687:126429. doi: 10.1016/j.ijpharm.2025.126429. Epub 2025 Nov 24.Int J Pharm. 2026.PMID: 41297864Review. * [ Ultrasonic approach for viscoelastic and microstructure characterization of granular pharmaceutical tablets. ](https://pubmed.ncbi.nlm.nih.gov/23820132/) Saeedi Vahdat A, Krishna Prasad Vallabh C, Hancock BC, Cetinkaya C.Saeedi Vahdat A, et al.Int J Pharm. 2013 Sep 15;454(1):333-43. doi: 10.1016/j.ijpharm.2013.06.045. Epub 2013 Jun 29.Int J Pharm. 2013.PMID: 23820132 * [ A review of the State-of-the-Art: progress in ultrasonic and acoustic techniques for quality assessment in the development and manufacturing of oral solid dosage forms - Part II: Applications and emerging directions. ](https://pubmed.ncbi.nlm.nih.gov/42055149/) Çetinkaya Ç, Bazzocchi M, Dave VS, Halkude B, Hussain AS, Prasad Vallabha CK, Razavi SM, Stephens J, Steiner R, Sultan T, Sun CC, Tantuccio AS, Tajarobi P, Ündey C, Wikström H, Xu X.Çetinkaya Ç, et al.Int J Pharm. 2026 Jun 5;698:126925. doi: 10.1016/j.ijpharm.2026.126925. Epub 2026 Apr 27.Int J Pharm. 2026.PMID: 42055149Review. 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