Northwest Missouri State University
Center for Innovation and Entrepreneurship
Faculty Research
Dr. Shelley Riley
Assistant Professor of Chemistry
GS 2643
660.562.1605
[email protected]
Area of Expertise
Education
Pharmaceutical Analysis (physical
chemical characterization of materials,
polymorphic screening/physical form
selection, stability studies, drug
delivery, and formulation development
for preclinical and clinical studies)
Ph.D. – Pharmaceutical Chemistry,
University of Kansas - Lawrence, KS
Courses Taught
•General Chemistry
•Instrumental Analysis
•Laboratory Safety
Select Publications
Rabel Riley, S.R.; Vickery, R.D.; Nemeth, G.A.; Haas,
M.J.; Kasprzak, D.J. Maurin, M.B. (2011). “Thermal
Decomposition of Matrix Metalloproteinase Inhibitors;
Evidence of a Solid State Dimerization” Journal of
Pharmaceutical and Biomedical Analysis, 54, 324-330.
Shanbhag, A.; Rabel, S.; Nauka,E.; Casadevall, G.;
Shivanand, P.; Eichenbaum, G.; Mansky, P. (2008).
“Method for screening of solid dispersion formulations of
low-solubility compounds—Miniaturization and automation
of solvent casting and dissolution testing” International
Journal of Pharmaceutics, 351, 209-218.
Radesca, L.; Moore, J.R.; Rabel, S.R.; and Maurin M.B.,
Crystalline Efavirenz. Patent 6673372, Jan. 6, 2004.
Maurin M.B., Vickery R.D., Rabel S.R., Rowe S.M., Everlof
J. G., Nemeth G.A., Campbell G.C., and Foris, C.M. (2002)
“Polymorphism of Roxifiban” Journal of Pharmaceutical
Sciences, 19(12), 2599-604.
Rabel Riley, S.R.; Parsons Jr., R.; and Patel M. Crystalline
(-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-3,4dihydro-2(1H)-quin azolinone. Patent 6225317, May 1,
2001.
Rabel, Shelley R., Jona, Janan A., and Maurin, Michael B.
(1999). “Applications of Modulated Differential Scanning
Calorimetry in Preformulation Studies” Journal of
Pharmaceutical and Biomedical Analysis, 21, 339-345.
Current Research
Preparation and Analytical Characterization of Nanosuspensions for Poorly Water Soluble Pharmaceuticals
The utilization of high-throughput
combinatorial screening methods in
pharmaceutical discovery has resulted
in the identification of drug molecules
of very high potency and selectivity
for potentially therapeutically
relevant receptors. Unfortunately,
the optimization of these biological
properties are often obtained at the
expense of other physical chemical
properties of the compound, such
as aqueous solubility, which are
required for successful development
of a formulation with acceptable
in-vivo performance. Formulation
and analytical challenges in
Pharmaceutical Research and
Development are extensive for these
compounds. One option to address
poorly water soluble drugs is to
reduce the particle size below the
1 μm level to obtain nanoparticles.
Dr. Riley’s current research is in the
area of preparation and analytical
characterization of nanosuspension
formulations of pharmaceutically
active compounds.
Although nanosuspensions may
be prepared relatively easily,
the challenge in formulation
development is to identify a
formulation that will be physically
stable without any particle size
growth over the shelf-life of a
product. Currently optimization of
nanosuspension formulations is a
trial and error method performed
by adding various stabilizers to
formulations and determining the
long term stability of formulations
using analytical methods such
as particle size analysis and
microscopy techniques. An area
of focus of Dr. Riley’s research is
to use analytical methods such
as particle size analysis, zeta
potential analysis, and atomic
force microscopy to evaluate
intermolecular interactions (steric
and electrostatic in nature) in
nanosuspensions to help aid in the
selection of stabilizers that would
be predicted to result in stable
formulations.
Figure 1. DSC thermogram of Naproxen recovered from
nanosuspension in Lutrol F68. Endotherm at 157 °C
matches that of the naproxen “as received”.
Preliminary work using Naproxen
as a model compound, evaluated
the stability of nanosuspensions
using a variety of non-ionic and ionic
stabilizers at concentration levels of
1 and 3% (w/v) at room temperature
and 4 °C. X-ray powder analysis and
Differential Scanning Calorimetry
of the naproxen “as received” and
“recovered from nanosuspensions”
indicated no change in the
polymorphic form of the compound
during the preparation or storage of
nanosuspensions. (Figure 1) Sodium
dodecyl sulfate and Polysorbate 80
were not effective as stabilizers,
whereas all formulations with Kollidon
VA64, Lutrol F68, and Methocel E6
were stable resulting in mean particle
sizes in the of less than 200 nm based
on a volume distribution.(Figure 2)
Additional studies will now be used
to measure the zeta potential, and
obtain images by AFM, and SEM
to probe the surface interactions of
the nanoparticles in an attempt to
rationalize the stability of the naproxen
nanosuspensions.
Figure 2. Representative particle size distribution based on volume for
a suspension of Naproxen in 3% Methocel E6 after16 days at room
temperature.