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Praveen Prasanna
Degree: Ph.D., Chemical Engineering
Advisor: Gregory Botsaris
Research Project: Directing the
crystallization of a desired polymorph
through secondary nucleation (seeding)
Project Description:
A large number of substances, including
high-value added pharmaceutical products,
crystallize in more than one distinct
crystal structures. These structures termed
polymorphs, display different physical
properties (solubility, crystal form,
density, compressibility, etc.) and
consequently pharmacological activities.
Regulatory pressure for the development of
consistent production processes, dictate the
need for a better understanding of all the
crystallization steps involved in the
process. The outcome at the primary
nucleation step is described by the
Ostwald’s “Rule of Stages,” which states
that the stable polymorph has the lowest
solubility and yet the metastable form of
higher solubility nucleates first.
It appears, however, that things are much
more complex in the case of secondary
nucleation. Recent studies1, 2
involved the crystallization of L-glutamic
acid which has two polymorphs: the stable
beta-form and the metastable alpha-form.
Seeds of the latter polymorph were used but
the resulting secondary nuclei were not
necessarily alpha polymorph. For instance,
at a certain supersaturation beta-polymorph
was obtained while at another a mixture of
alpha and beta was produced. The case of
epitaxial growth of beta on alpha was also
reported.
Our work is a systematic investigation of
secondary nucleation in the crystallization
of L-glutamic acid. Seeds of both polymorphs
are used at different supersaturations and
temperatures. The crystals resulting from
the secondary nuclei are collected and their
crystalline structure is obtained by melting
point measurements and an x-ray diffraction
technique.
The interpretation of the results is based
on the solubility data of the two polymorphs
and two mechanisms of secondary nucleation:
the Contact Secondary Nucleation (CSN) and
the Embryos-Coagulation Secondary Nucleation
(ESCN) model. The ESCN model wad developed
by Qian and Botsaris3, 4 and was
successfully used to direct the
crystallization of crystals of a desired
chirality in the cases of sodium chlorate
and threonine.
1. Cashell C, Corcoran D, Hodnett BK.
Secondary nucleation of the b-polymorph of
the L-glutamic acid on the surface of a-form
crystals. Chem Commun. 2003:374-375.
2. Ferrari ES, Davey RJ. Solution-mediated
transformation of a to b L-glutamic acid:
Rate enhancement due to secondary
nucleation. Cryst Growth Des. Sep-Oct
2004;4(5):1061-1068. 3. Qian R-Y, Botsaris
GD. A new mechanism for nuclei formation in
suspension crystallizers: the role of
interparticle forces. Chem Eng Sci.
1997;52(20):3429-3440.
4. Qian R-Y, Botsaris GD. The effect of seed
preparation on the chirality of the
secondary nuclei. Chem Eng Sci.
2004;59:2841-2852.
Education & Experience:
Bachelor of Engineering (Chemical
Engineering), McGill University, 1996.
Master of Engineering (Chemical
Engineering), McGill University, 1998.
Professional Engineer, Quebec, 2000
Process Engineer,
RTP
Pharma (now part of SkyePharma), Monteal,
1998-1999
Process Engineer, Wyeth Biopharma,
Andover, Mass., 2000-2002.
Funding:
Tufts University
Publications:
P.Prasanna and GD Botsaris.
Directing the Crystallization of a Desired
Polymorph through Secondary Nucleation
(Seeding). AIChE Annual Meeting, San
Francisco, CA; (2006). |
Graduate Students:
Fernando Lima
Foteini Makrydaki
Praveen Prasanna
Lisa Schupmann
Sze Wing Wong |
