Evidence mapPaperPMID 42086873Full record

ArticlePharmaceutical research2026

Thermally Stressed Solid-State Stability of Semaglutide: Understanding the Influence of Temperature on Protein Content, Secondary Structure, Phase Transition, and Chemical Degradation.

Sideequl Akbar, Adarsh Malgave, Anumol Joseph, Ankit Kumar, Rajkumar Malayandi

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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

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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

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Sideequl AkbarDepartment of Pharmaceutics, Export Promotion Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Hajipur, Zandaha Road NH322, Hajipur, 844102, Bihar, India.ORCID http://orcid.org/0009-0000-2371-3239
Adarsh MalgaveDepartment of Pharmaceutics, Export Promotion Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Hajipur, Zandaha Road NH322, Hajipur, 844102, Bihar, India.ORCID http://orcid.org/0009-0007-8970-7000
Anumol JosephDepartment of Pharmaceutics, Export Promotion Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Hajipur, Zandaha Road NH322, Hajipur, 844102, Bihar, India.ORCID http://orcid.org/0009-0000-8802-0089
Ankit KumarDepartment of Pharmaceutics, Export Promotion Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Hajipur, Zandaha Road NH322, Hajipur, 844102, Bihar, India.ORCID http://orcid.org/0009-0002-0603-1492
Rajkumar MalayandiDepartment of Pharmaceutics, Export Promotion Industrial Park (EPIP), National Institute of Pharmaceutical Education and Research, Hajipur, Zandaha Road NH322, Hajipur, 844102, Bihar, India. rajkumar.ceutics@niperhajipur.ac.in.ORCID http://orcid.org/0000-0003-1435-6115

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveSemaglutide (SMG), a clinically relevant peptide-based therapeutic whose physical and chemical stability are critical concerns during manufacturing and storage. Although the stability of SMG in solution has been extensively studied, its solid-state behaviour remains unclear. This study aimed to systematically evaluate the impact of thermal stress on the solid-state physicochemical stability of SMG.

methodsThe solid-state stability of SMG was assessed using complementary analytical techniques, including Fourier transform-infrared (FT-IR) spectroscopy, circular dichroism (CD), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), reverse-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS).

resultsFT-IR and CD analyses demonstrated that SMG retains its native α-helical conformation up to 60°C. However, the α-helical content decreased from 49.07% to 43.75% at 60°C and further to 0.2% at 80°C, indicating extensive conformational transitions at elevated temperatures that compromise receptor binding and in vivo performance. DSC and HSM confirmed that SMG remains amorphous under all tested conditions and revealed three major thermal events: residual water loss, enthalpy recovery associated with physical ageing, and thermal decomposition. The overlap of enthalpy recovery with the glass transition phase limited the determination of Tg by conventional DSC; however, modulated DSC enabled the separation of these events, establishing a Tg of 169°C. RP-HPLC and LC-HRMS analyses showed a temperature-dependent degradation and impurity formation.

conclusionThe solid-state stability study identified temperature as a critical factor influencing SMG stability and emphasises the importance of stringent process control in the development of SMG-based formulations.

Indexed as

SemaglutideCalorimetry, Differential ScanningChromatography, High Pressure LiquidCircular DichroismDrug StabilityHot TemperaturePhase TransitionProtein Structure, SecondarySpectroscopy, Fourier Transform InfraredTemperatureSemaglutideenthalpy recoveryimpurity profilingmolecular relaxationsemaglutidesolid-state stabilityα-helical peptide

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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 Socratic graph.