Related Experiment Video

Updated: May 11, 2026

Formulations for Freeze-drying of Bacteria and Their Influence on Cell Survival
08:55

Formulations for Freeze-drying of Bacteria and Their Influence on Cell Survival

Published on: August 3, 2013

Controlling the physical form of mannitol in freeze-dried systems

Mehak Mehta1, Sunny P Bhardwaj, Raj Suryanarayanan

  • 1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, USA.

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V
|May 7, 2013
PubMed

Insights

Mannitol hemihydrate (MHH) formation during freeze-drying can destabilize products. Controlling ice crystallization temperature prevents MHH, ensuring product stability by promoting anhydrous mannitol formation.

Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Physical Chemistry

Background:

  • Mannitol is a common bulking agent in lyophilized formulations.
  • Mannitol can exist as anhydrous mannitol or mannitol hemihydrate (MHH) in the lyophile.
  • MHH formation during freeze-drying can lead to product instability due to water release during secondary drying or storage.

Purpose of the Study:

  • To identify the crystallization conditions of anhydrous mannitol and MHH.
  • To prevent MHH formation during freeze-drying processes.
  • To ensure the stability of lyophilized products.

Main Methods:

  • Systematic investigation of mannitol crystallization in frozen systems.
  • Low-temperature X-ray diffractometry (laboratory and synchrotron sources).
  • Utilizing controlled ice nucleation technology in freeze-drying.

Main Results:

  • Mannitol's crystalline form depends on solute crystallization temperature.
  • MHH forms when crystallization occurs at or below -20 °C.
  • Anhydrous mannitol forms when crystallization occurs at or below -10 °C.
  • Controlled ice nucleation enabled anhydrous mannitol crystallization at approximately -5 °C.

Conclusions:

  • Solute crystallization temperature is critical for determining mannitol's physical form.
  • Preventing MHH formation is achievable by controlling crystallization temperatures.
  • Ice crystallization followed by annealing below -10 °C effectively prevents MHH formation, enhancing product stability.
Keywords:
AnnealingControlled ice nucleationFreeze-dryingMHHMannitolMannitol hemihydrateSynchrotron XRDX-ray diffractometryXRD

More Related Videos

Growing Protein Crystals with Distinct Dimensions Using Automated Crystallization Coupled with In Situ Dynamic Light Scattering09:15

Growing Protein Crystals with Distinct Dimensions Using Automated Crystallization Coupled with In Situ Dynamic Light Scattering

Published on: August 14, 2018

Optimization of Crystal Growth for Neutron Macromolecular Crystallography12:29

Optimization of Crystal Growth for Neutron Macromolecular Crystallography

Published on: March 13, 2021

Related Concept Videos

Crystal Growth: Principles of Crystallization01:25

Crystal Growth: Principles of Crystallization

Crystallization is a phase transformation process in which crystals are precipitated from a supersaturated solution or formed from other sources. During crystallization, atoms or molecules arrange themselves into a well-defined, rigid crystal lattice to minimize energy.
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent – the...
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Precipitate Formation and Particle Size Control01:16

Precipitate Formation and Particle Size Control

In precipitation gravimetry, the precipitating agent should react specifically or selectively with the analyte. While a specific reagent reacts with the analyte alone, a selective reagent can react with a limited number of chemical species.
The obtained precipitate should be either a pure substance of known composition or easily converted to one by a simple process, such as ignition or drying. In addition, the precipitate should be insoluble and easily filterable. In general, filterability...
Recrystallization: Solid–Solution Equilibria01:10

Recrystallization: Solid–Solution Equilibria

Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...