taPrime Consulting Ltd

taPrimer Archive

taPrimers are the short articles that appear on this website to highlight aspects of the freeze drying process.  Missed some of them?  No problem, just follow the individual links below.

The Shape of the Glass Transition  
A glass transition is quite unlike a melting point or boiling point. The value measured depends upon the method used, yet all vaues are equally valid. To understand the glass transition, why it has its familiar S-shaped step in the DSC heat flow, or why relaxation enthalpy recovery can alter the shape, download The Glass Transition.

Controlled Nucleation and Synchronised Freezing
Little attention is usually paid to the freezing step of freeze drying, but controlled nucleation and top down freezing are claimed to improve sublimation times.  Download Synchronised_Freezing for an overview of the technology and a simple way to test the potential benefits on a lab scale. 

Can cold labile proteins be freeze dried?
Yes they can but loss of activity on freezing is more likely to be due to freeze concentration than cold lability. This taPrimer discusses the little known phenomenon of low temperature unfolding (denaturation) and how this differs significantly from the better known high temperature denaturation. If you think you have a cold labile protein but would like to freeze dry it then read Cold labile proteins.

Freezing and low temperature have nothing to do with each other!
Freezing and low temperature are different phenomena and the advantages of low temperature can easily be outweighed by the disadvantages of freezing. Interested in knowing more?  Check out our Freezing primer.

The Physics of freezing.
Have you ever wondered why water never freezes at its freezing point, or why your vials all freeze at different times and temperatures?  Perhaps even why your DSC samples freeze at lower temperatures than the same solution in a vial?  Although we often talk about the freezing point of water, in fact, water does not have a unique and reproducible freezing point.  Interested in knowing more?  See our taPrimer The Physics of Freezing.

Freezing: does it lead to crystals, glasses or both?
Primary drying, the removal of ice by sublimation must be carried out below the collapse temperature (Tc). But what exactly is the collapse temperature? Depending on the freezing behaviour of the product, Tc sometimes represents a eutectic melting temperature and sometimes the glass transition temperature. Our taPrimer Freezing Behaviour explains the different types of freezing behaviour you may encounter and what the consequences are for freeze drying development.

Confused about collapse temperature, Tg, Tg', or Tg''?
If you are not sure of the difference between Tg, Tg' or Tg'', let alone collapse temperature, then download our Tg primer.

Tg' and Tg''
The fact that the term glass transition can refer to two different events can be confusing, but our taPrimer Mind the gap explains the difference and discusses the importance of  Tg' and Tg'', or Tc and Tg, for the freeze drying process.

Ice sublimation and pressure
Increasing the pressure increases the rate of ice sublimation, but so does decreasing the pressure.  Intrigued?  Download our  Feeling the Pressure Primer.

What is Dry?
A sugar that contains 15 % w/w water, an amorphous glass that contains equimolar amounts of water and carbohydrate and a protein glass that contains 20 moles of water per mole of protein can all be described as dry!  Download our What is dry? primer to find out why.

Mannitol
Despite being one of the most commonly used excipients, mannitol probably leads to more problems than any other additive. Download our Mannitol primer to see what makes it different to other excipients and how to avoid the all too common problems.

Trehalose: Myth, Magic or Materials Science?
In the past exceptional claims were made about the unique properties of trehalose as a stabiliser. In Trehalose: Myth, Magic or Materials Science? we explain why trehalose is a useful but neither unique nor exceptional excipient.
 

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