# Nucleation in Amorphous Terfenadine at a Temperature Much Lower than the Glass Transition Temperature and Its Impact on Physical Stability

https://mdr.nims.go.jp/datasets/d59c8a0e-108f-4bbe-87f4-473f001e0807

## Files

- [2025MolPharm_TFD.pdf](https://mdr.nims.go.jp/filesets/2cb66f8d-de2a-4a17-b567-72fe44ce421c/download) ([Detail](https://mdr.nims.go.jp/filesets/2cb66f8d-de2a-4a17-b567-72fe44ce421c.md))

## Id

d59c8a0e-108f-4bbe-87f4-473f001e0807

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2025-11-21T09:21:02.870600Z

## Updated at

2025-11-25T03:30:07.545353Z

## Published at

2025-11-25T03:23:33.777980Z

## Doi



## First published url

https://doi.org/10.1021/acs.molpharmaceut.5c00700

## Date published

2025-10-06

## Recorded date published

2025-10-6

## Resource type

journal_article

## Manuscript type

vor

## Collection



## Title

- title: Nucleation in Amorphous Terfenadine at a Temperature Much Lower than the
    Glass Transition Temperature and Its Impact on Physical Stability
  title_type: original
  lang: en

## Description

- description: " In this study, the crystallization behavior of amorphous terfenadine
    (TFD) was investigated with a focus on\r\nnucleation temperature. The cold crystallization
    behavior of amorphous TFD annealed at various\r\ntemperatures and the resultant
    crystal form were evaluated by using differential scanning calorimetry and powder
    X-ray diffraction. Samples annealed at −20°C provided the lowest cold crystallization
    temperature and the highest proportion of form II, indicating that nucleation
    for form II was enhanced at a temperature much lower than the glass transition
    temperature (58 °C). Initiation time for isothermal crystallization of TFD at
    100 °C was shortened by 30% by applying annealing at −20 °C beforehand. In contrast,
    dissolution\r\nand supersaturation behaviors were not affected by nucleation,
    as the crystal form of the precipitate was different from that induced by annealing.
    The isoconversional Kissinger−Akahira−Sunose model was applied to analyze the
    cold crystallization kinetics to find an increase in the apparent frequency factor
    for samples annealed at −20 °C, suggesting the presence of preformed crystal nuclei.\r\nLastly,
    the anomalous nucleation behavior of amorphous TFD at low temperatures was discussed
    from the framework of classical nucleation theory and molecular mobility. This
    study provides important insights into the nucleation and crystal growth behaviors
    of amorphous pharmaceutical compounds."
  description_type: abstract
  lang: und

## Creator

- name: Katsutoshi Yamaguchi
  role: author
- name: Yuya Ishizuka
  role: author
- name: Etsushi Yoshikawa
  role: author
- name: Takashi Makishima
  role: author
- name: Ryo Mizoguchi
  role: author
- name: Kohsaku Kawakami
  role: author
  orcid: https://orcid.org/0000-0002-3466-9365
  organization: National Institute for Materials Science

## Contact agent



## Publisher

organization: American Chemical Society (ACS)

## Managing organization



## Keyword

- subject: amorphous
  schema: not_defined
- subject: nucleation
  schema: not_defined
- subject: crystal growth
  schema: not_defined
- subject: physical stability
  schema: not_defined
- subject: local molecular mobility
  schema: not_defined

## Rights

- identifier: https://creativecommons.org/licenses/by/4.0/

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo



## Journal

- title: Molecular Pharmaceutics
  issn: '15438392'
  volume: '22'
  issue: '10'
  start_page: 6038
  end_page: 6049

## Conference



## Related item



## Funding

- funder_name: National Institute for Materials Science

## Instrument



## Instrument operator



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## Measurement method



## Specimen



## Chemical composition



## Structure for specimen



## Structural feature for specimen



## Specific property for specimen



## Process for specimen treatment



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## Fileset

- id: 2cb66f8d-de2a-4a17-b567-72fe44ce421c
  filename: 2025MolPharm_TFD.pdf
  content_type: application/pdf
  size: 3855244
  md5: 8e976c53d770a6c2dea7c0bbfa547a67

## Thumbnail

fileset_id: 2cb66f8d-de2a-4a17-b567-72fe44ce421c
filename: 2025MolPharm_TFD.pdf