Mutual Influence of Mannitol and Trehalose on Crystallization Behavior in Frozen Solutions

Pharmaceutical Research
Sampreeti JenaAlptekin Aksan

Abstract

Phase separation of trehalose during freeze-drying could render it ineffective as a lyoprotectant. The bulking agent, mannitol, on the other hand, should crystallize readily upon freezing. It is therefore imperative to understand the mutual interaction of these sugars during freezing to ensure preservation of the API during freeze-drying. We investigated the effect of mannitol to trehalose ratio (R) on the crystallization behavior of both solutes using Differential Scanning Calorimetry, X-Ray Crystallography and FTIR Spectrosopy during controlled freezing and annealing. When R = 1, crystallization of both mannitol (as hemihydrate) and trehalose (as α-anhydrate) were observed. When R ≥ 1, extent of mannitol crystallization was directly proportional to the value of R. When R < 1, trehalose completely suppressed mannitol crystallization. At R > 1, the freeze concentrate was heterogeneous and characterized by two glass transitions - the lower temperature transition (Tg") attributed to systems containing "extra" unfrozen water. When heated above Tg", crystallization of mannitol and the associated unfrozen water resulted in Tg' (glass transition temperature of the freeze-concentrate). R and not the total solute concentration, dictate...Continue Reading

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Citations

Jun 11, 2016·International Journal of Pharmaceutics·Ken-Ichi IzutsuKatsuhide Terada
May 20, 2014·International Journal of Pharmaceutics·Mehulkumar PatelArvind K Bansal
Jan 3, 2012·Advanced Drug Delivery Reviews·Prakash Sundaramurthi, Raj Suryanarayanan
May 7, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mehak MehtaRaj Suryanarayanan
Dec 17, 2016·Pharmaceutical Research·Sampreeti JenaAlptekin Aksan
Oct 29, 2018·Advanced Healthcare Materials·Congzhou WangSrikanth Singamaneni
Nov 27, 2018·Biotechnology and Bioengineering·Chia-Hsing PiAllison Hubel
Jul 29, 2019·International Journal of Pharmaceutics·Sampreeti JenaRaj Suryanarayanan
Mar 21, 2021·Advanced Drug Delivery Reviews·Seema ThakralRaj Suryanarayanan
Aug 30, 2019·Journal of Pharmaceutical Sciences·Yoann Le BasleValérie Sautou

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