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Steven P. Stodghill earned a B.S. in Pharmacy from the University of Mississippi in 1989 and completed an A.S.H.P. residency at the University of Cincinnati Medical Center in 1990. After practicing for four years he returned to the University of Mississippi where he earned a Ph.D. in 2000. He joined the faculty at the University of Mississippi in the Summer of 2000 as an assistant professor of pharmaceutics and an assistant research professor of the research institute of pharmaceutical sciences.
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at the University of Mississippi, Department of Pharmaceutics
The
primary focus of our research group is in the solid-state chemistry of
pharmaceuticals and nutraceuticals as well as the development of novel
advanced drug delivery systems. Current research projects include
the characterization of the physical properties of both pure compound and
formulations in the solid-state using techniques and instrumentation described
below with an emphasis on formulations utilizing hot-melt extrusion technology.
Additionally our group has received funding to pursue the development of
a novel drug delivery system utilizing a relatively new technique referred
to as adsolubilization. This technique takes advantage of a new admicelle
system we are developing which in theory should greatly increase the bioavailability
and stability of compounds with poor aqueous solubility. Admicelles
and adsolubilization can be thought of as the surface analogues to micelles
and their solubilization capacity. In theory any compound with poor
aqueous solubility could be adsolubilized with this system however to date
all work has been done with model drug compounds to show proof of concept
and we are in the process of identifying several drug candidates for future
studies.
A summary of our analytical instrumentation and research capabilities is
given below.
ANALYTICAL CAPABILITIES
Thermal Analysis: DSC and TGA
Our lab currently uses the Perkin-Elmer Pyris1 Differential Scanning Calorimeter
(DSC) and Pyris-1 Thermogravimetric Analyzer (TGA) systems. These
instruments allow for the monitoring of thermochemical events and weight
loss as a function of temperature and thus provide valuable insight into
solid form characteristics, solid-state degradation pathways and mechanisms
of polymorphic transformations. The DSC is equipped with the optional
Step Scan® accessory which allows for better identification
and interpretation of glass transitions.
Thermal Analysis: Isothermal Titration Calorimetry (ITC)
ITC is a thermodynamic technique for monitoring the heat of reactions for
a wide variety of chemical phenomena. Currently a Microcal VP-ITC
Microcalorimeter is used by our lab for these studies. We have extensive
experience in applying this technique to the study of cyclodextrin binding
with numerous compounds and in generating adsorption isotherms for the
binding of surfactants and polymers to silica substrates. Additionally
we are developing techniques to study the thermodynamics of adsolubilization.
Particle Size Distribution and Analysis:
A Beckman Coulter LS 13 320 Multi-Wavelength Particle Size Analyzer is
currently used to perform particle size distribution and analysis.
The system is equipped with a Universal Liquid Module which allows for
the analysis of both water soluble and insoluble compounds. This
system is capable of analyzing samples with a particle size in the range
of 0.04 µm to 2000 µm.
Surface Area Analyzer:
A Quantachrome Nova 1200 surface area analyzer is currently used to conduct
studies regarding surface area calculations as well as density and porosity
studies. This instrument can use a variety of adsorbents and provides
data regarding BET isotherms and their interpretations.
Polarized Light Microscopy:
We currently perform polarized light microscopy using a LOMO®
Polam-L 213-BE microscope. This system is equipped with digital
imaging capabilities as well as particle size and distribution software.
Our lab plans to add hot-stage microscopy capabilities in the near future.
Scanning Electron Microscopy
The Department of Pharmaceutics at the University of Mississippi has recently
acquired a JOEL 5600 SEM which is available to our group for SEM imaging.
Wide-angle X-ray Diffraction (WAXRD)
The Department of Pharmaceutics at the University of Mississippi has also
recently acquired a Bruker D8 Advanced X-ray diffractometer with a SOL-X
detector which is available to our group for XRD work.
Molecular Modeling:
Our lab has experience in molecular modeling of the solid-state including
molecular dynamics simulations using Materials Studio®
from Accelrys. We also have access to SGI®
hardware running a variety of molecular modeling packages including, SYBYL®,
Spartan®, and MacroModel®,
all of which include access to several molecular mechanic, semi-empirical
and empirical force fields.
IR/NIR Spectroscopy:
Our lab also has access to a Bruker Equinox 55 IR/NIR spectrometer which
is also equipped with fiber optics. These spectroscopy techniques
can provide both qualitative characterizations of different solid forms
and quantitative methods to determine the solid form composition within
the drug substance or product.
RESEARCH CAPABILITIES:
Solid Form Identification and Characterization:
The identification of a drug substances specific solid form including,
polymorphs, hydrates, solvates, and amorphous forms, is a crucial step
in characterizing a new compound. Our group presently utilizes state
of the art thermal analysis equipment and procedures for solid form identification
and characterization.
Determination of Optimal Solid Form:
Once the solid forms have been identified and characterized the optimal
solid form for further development must be determined. Not only must
the optimal form be identified but analytical techniques must be in place
to insure that the desired solid form is what is being produced and maintained
especially after formulations have been developed and scale-up has started.
Chemical and Physical Stability of Solid Forms:
Accelerated stability studies in the solid-state are always challenging
due to the nature of the sample. Mechanisms and rates of degradation
are greatly affected by the solid form especially polymorphs and solvates
as well as by changes in crystal lattice type and particle size.
Our lab currently conducts stability studies using elevated temperature
and humidity techniques as well as isothermal and nonisothermal kinetic
studies using DSC and TGA.
Composition as a Function of Relative Humidity:
The water sorption profile of a solid provides key information regarding
the physical stability of hydrated forms. Our lab investigates the
hygroscopicity at various relative humidities and temperatures using dynamic
methods as well as traditional static methods.
Stabilization of Drug Candidates and Dosage Forms:
The stabilities of pure compound compared to a complete formulation can
be quite different. In addition, unstable solid forms such as amorphous
solids must be stabilized in order to develop a successful formulation.
Through the studies conducted in our lab we intend to not only find methods
for stabilizing these compounds but also pursue methods for predicting
potential problems early in the discovery phase.
Through collaborations with other members in our department our lab has
the capability, when needed, to conduct additional characterization studies.
These studies include, analysis of active drug in dosage forms, dissolution
and solubility testing, and establishing bulk material specifications.
Statistical Analysis and Data Interpretation:
As a result of the work underway in our lab, our group has extensive experience
in statistical analysis and data interpretation particularly in the areas
of chemical kinetic and pharmacokinetic data. This has resulted in
several consultation and collaborative opportunities for our group.
We currently use GraphPad
Prism ® software for statistical analysis
and advanced model fitting and interpretation using nonlinear regression
techniques.