The effect of water plasticization on the molecular mobility and crystallization tendency of amorphous disaccharides

Ville Petteri Heljo (Corresponding Author), Antti Nordberg, Mikko Tenho, Tommi Virtanen, Kirsi Jouppila, Jarno Salonen, Sirkka Liisa Maunu, Anne Mari Juppo

Research output: Contribution to journalArticleScientificpeer-review

36 Citations (Scopus)

Abstract

Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, whichmay have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

Original languageEnglish
Pages (from-to)2684-2697
Number of pages14
JournalPharmaceutical Research
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Melibiose
Disaccharides
Cellobiose
Crystallization
Trehalose
Sucrose
Water
Water content
Sorption
Transition Temperature
Excipients
Humidity
Atmosphere
Relaxation time
Drug products
Glass
Atmospheric humidity
Crystalline materials
Temperature
Pharmaceutical Preparations

Keywords

  • Amorphous
  • Crystallization
  • Disaccharide
  • Mobility
  • Water

Cite this

Heljo, Ville Petteri ; Nordberg, Antti ; Tenho, Mikko ; Virtanen, Tommi ; Jouppila, Kirsi ; Salonen, Jarno ; Maunu, Sirkka Liisa ; Juppo, Anne Mari. / The effect of water plasticization on the molecular mobility and crystallization tendency of amorphous disaccharides. In: Pharmaceutical Research. 2012 ; Vol. 29, No. 10. pp. 2684-2697.
@article{e8f05bffebeb4670bd6899c17c4900aa,
title = "The effect of water plasticization on the molecular mobility and crystallization tendency of amorphous disaccharides",
abstract = "Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, whichmay have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.",
keywords = "Amorphous, Crystallization, Disaccharide, Mobility, Water",
author = "Heljo, {Ville Petteri} and Antti Nordberg and Mikko Tenho and Tommi Virtanen and Kirsi Jouppila and Jarno Salonen and Maunu, {Sirkka Liisa} and Juppo, {Anne Mari}",
year = "2012",
month = "10",
doi = "10.1007/s11095-011-0658-4",
language = "English",
volume = "29",
pages = "2684--2697",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer",
number = "10",

}

The effect of water plasticization on the molecular mobility and crystallization tendency of amorphous disaccharides. / Heljo, Ville Petteri (Corresponding Author); Nordberg, Antti; Tenho, Mikko; Virtanen, Tommi; Jouppila, Kirsi; Salonen, Jarno; Maunu, Sirkka Liisa; Juppo, Anne Mari.

In: Pharmaceutical Research, Vol. 29, No. 10, 10.2012, p. 2684-2697.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The effect of water plasticization on the molecular mobility and crystallization tendency of amorphous disaccharides

AU - Heljo, Ville Petteri

AU - Nordberg, Antti

AU - Tenho, Mikko

AU - Virtanen, Tommi

AU - Jouppila, Kirsi

AU - Salonen, Jarno

AU - Maunu, Sirkka Liisa

AU - Juppo, Anne Mari

PY - 2012/10

Y1 - 2012/10

N2 - Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, whichmay have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

AB - Purpose To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose. Methods Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants. Results Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, whichmay have partly been caused by its relatively slow molecular mobility. Conclusions Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

KW - Amorphous

KW - Crystallization

KW - Disaccharide

KW - Mobility

KW - Water

UR - http://www.scopus.com/inward/record.url?scp=84866731586&partnerID=8YFLogxK

U2 - 10.1007/s11095-011-0658-4

DO - 10.1007/s11095-011-0658-4

M3 - Article

C2 - 22203327

AN - SCOPUS:84866731586

VL - 29

SP - 2684

EP - 2697

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 10

ER -