INSIGHT - COMMENTS
Vol. 1 No. 3 Computer Modeling of the Lyophilization Process
I have read the last issue of the INSIGHT with great interest and I really appreciate this way of knowledge exchange and discussion; you started here an excellent publishing series.
But there is still an unanswered question that I am interested in: As you mentioned at the end of the last INSIGHT-volume under the column "secondary drying process" it is of fundamental interest to know the optimum residual moisture level for a given protein/peptide-formulation!
But how can I know this factor in advance I mean before I started lyophilization and examine the results afterwards (to say the influence of different process parameters on the quality of the final product)?
Of course there is on the one hand a well known range of too much residual moisture (detrimental shelf-life) and on the other hand of too less moisture (= "overdrying"). In my opinion it is nearly impossible to determine this (most) important product feature from "online" process data however the knowledge of an optimum residual moisture in advance is also of less value as long as I don´t know how far my process parameters do specifically influence this feature.
Isn´t it still a trial and error proceeding?
Thank you for your interest in advance!
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Tilman Rock
University of Heidelberg
Laboratory for Pharmaceutical Technology
Im Neuenheimer Feld 366
69120 Heidelberg
Germany
Tel.-Nr.: 06221 / 54-8332
Telefax: 06221 / 54-5971
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Response by T.A. Jennings
Regarding you questions concerning the optimum residual moisture in protein-peptide formulations. You are quite right that it is not possible with just knowledge of the excipients in the formulation to ascertain the correct range of moisture values in a cake prior to conducting a lyophilization process.
The stability of the protein or peptide will not only be dependent on the initial residual moisture content but also on the nature of the excipients. For example, if lactose were selected as an excipient, it may well compete for the residual moisture to form a hydrate at the expense of the moisture associated with the protein or peptide. The loss in moisture from a protein could result in a change in configuration and possible loss in activity. The point here is that not only must you know the correct range of moisture values but also the nature of the excipients. I agree with you that we are still reduced to using the "trial and error" method in ascertaining the correct range of moisture values for a lyophilized product. However, the more knowledge that one can obtain about the nature of a given protein or peptide perhaps we can select the excipients and the possible range of moisture values via an educated "guess". Writing a general computer program to determine the above appears not to be feasible at this time or at any time in the near future.
Vol. 1 No. 3 Computer Modeling of the Lyophilization Process
This is an eye-opener for people hoping that the computer will solve all problems. Freeze-drying inspite of being an apparently simple process is about impossible to handover to computers.
As you pointed out it is very difficult to define all the physical correlation. In operation computer cycles have known to have a problem about moving on till ALL the parameters are as expected and in case of any minor malfunction/breakdown can delay batch indefinitely.
Hiren Shah September 1998
EUTECTIC TECHNOLOGIES
9/42, Rupal, Garodia Nagar, Ghatkopar (E), Bombay -400 077,India.
Tel : 91 22 5139690 Telefax : 91 22 515 0744
"SWATI.PRAVINCHANDRA.SHAH" <sshah@giasbmc.vsnl.net.in>
Response by T.A. Jennings
Thank you for your comments.
