# Long-term physical stability of amorphous solid dispersions: Comparison of detection powers of common evaluation methods for spray-dried and hot-melt extruded formulations

https://mdr.nims.go.jp/datasets/4708348c-d0bd-4173-884d-d5ccd5db132f

## File

- [manuscript_JPS_FEN.docx](https://mdr.nims.go.jp/filesets/741a26bc-c902-4db0-9e2f-23b3f4669535/download) ([Detail](https://mdr.nims.go.jp/filesets/741a26bc-c902-4db0-9e2f-23b3f4669535.md))

## Id

4708348c-d0bd-4173-884d-d5ccd5db132f

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2025-04-30T01:15:44.575674Z

## Updated at

2025-06-28T23:30:20.026461Z

## Published at

2025-06-28T23:19:21.622175Z

## Doi

https://doi.org/10.48505/nims.5522

## First published url

https://doi.org/10.1016/j.xphs.2024.06.020

## Date published

2024-06-29

## Recorded date published

2025-1

## Resource type

journal_article

## Manuscript type

accepted_manuscript

## Collection



## Title

- title: 'Long-term physical stability of amorphous solid dispersions: Comparison
    of detection powers of common evaluation methods for spray-dried and hot-melt
    extruded formulations'
  title_type: original
  lang: en

## Description

- description: Although physical stability can be a critical issue during the development
    of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect
    their physical stability. In this study, we have prepared fenofibrate ASDs using
    two representative manufacturing methods, hot-melt extrusion and spray-drying,
    to investigate their physical stability for one year. Intentionally unstable ASDs
    were designed to compare the detection power of each evaluation method, including
    X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning
    electron microscopy (SEM), and dissolution study. Each method did not provide
    the same judgment results on physical stability in some cases because of their
    different evaluation principles and sensitivity, which has been well-comprehended
    only for one-component glass. This study revealed that the detection powers of
    each evaluation method significantly depended on the manufacturing methods. DSC
    was an effective method to detect a small amount of crystals for both types of
    ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower
    compared to that of DSC, interpretation of the data was the easiest. SEM was very
    effective for observing the crystallization of the small amount of drug for hot-melt
    extruded products, as the drug crystal vividly appeared on the large grains. The
    dissolution performance of spray-dried products could change even without any
    indication of physical change including crystallization. The advantage/disadvantage
    and complemental roles of each evaluation method are discussed for deeper understanding
    on the physical stability data of ASDs.
  description_type: abstract
  lang: und

## Creator

- name: Kohsaku Kawakami
  role: author
  orcid: https://orcid.org/0000-0002-3466-9365
- name: Taichi Ishitsuka
  role: author
- name: Masafumi Fukiage
  role: author
- name: Yohei Nishida
  role: author
- name: Tetsuo Shirai
  role: author
- name: Yosuke Hirai
  role: author
- name: Tetsu Hideshima
  role: author
- name: Fumiaki Tanabe
  role: author
- name: Koji Shinoda
  role: author
- name: Ryota Tamate
  role: author
  orcid: https://orcid.org/0000-0002-1704-1058
- name: Takuya Fujita
  role: author

## Contact agent



## Publisher

organization: Elsevier BV

## Managing organization



## Keyword

- subject: Amorphous solid dispersion
  schema: not_defined
- subject: Crystallization
  schema: not_defined
- subject: Stability
  schema: not_defined
- subject: Dissolution study
  schema: not_defined

## Rights

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

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo

start_date: 2024-06-29
end_date: 2025-06-29

## Journal

- title: Journal of Pharmaceutical Sciences
  issn: '00223549'
  volume: '114'
  issue: '1'
  start_page: 145
  end_page: 156

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## Fileset

- id: 741a26bc-c902-4db0-9e2f-23b3f4669535
  filename: manuscript_JPS_FEN.docx
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  size: 8164123
  md5: bdeb6e705179cc1ed926eda60e196b6f

## Thumbnail

fileset_id: 741a26bc-c902-4db0-9e2f-23b3f4669535
filename: manuscript_JPS_FEN.docx