Changquan Calvin Sun Lab

Pharmaceutical Materials Science and Engineering Laboratory

Department of Pharmaceutics
College of Pharmacy, University of Minnesota

Our research focuses on manufacturing science of solid dosage forms, such as tablets and capsules. Formulation and process development is achieved by a clear scientific understanding of powders, including their flow and compaction properties. In this way, design replaces trial and error, and improved quality results.

We rely on three levels of control to attain the desired powder properties for successful manufacturing: (1) study and specification of the physico-mechanical properties of drugs; (2) incorporation of appropriate excipients for optimum mechanical properties; and (3) optimization of processes such as mixing, granulation, and compaction, based on a mechanistic understanding.

People

Dr. Changquan Calvin Sun – Lab Supervisor, sunx0053@umn.edu

Mr. Hongbo Chen – PhD Student (Sept. 2015-Present), chen4515@umn.edu
Ms. Joan Cheng – PhD Student (Sept. 2019-Present), cheng842@umn.edu
Mr. Jiangnan Dun – PhD Student (Sept. 2014-Present), dunxx004@umn.edu
Ms. Yiwang Guo – PhD Student (Jan. 2016-Present), guoxx836@umn.edu
Ms. Shenye Hu – PhD Student (Sept. 2014-Present), huxxx839@umn.edu
Ms. Zhengxuan Liang – MS Student (Sept. 2018-Present), liang650@umn.edu
Dr. Manish Mishra – Post-Doctoral Associate (August 2018-Present), mmishra@umn.edu
Mr. Gerrit Vreeman – PhD Student (Sept. 2018-Present), vreem012@umn.edu
Dr. Chenguang Wang – Post-Doctoral Associate (June 2016-Present), wang4889@umn.edu
Ms. Kunlin Wang – PhD Student (Sept. 2015-Present), wang3248@umn.edu
Mr. Shan Wang – Visiting Scholar (Nov. 2019-Present), wang9664@umn.edu
Prof. Jun Wen – Visiting Scientist (May 2019-Present), wen00065@umn.edu

Past Members

Dr. Shao-Yu Chang – PhD Student (Sept. 2012-May 2019)
Dr. Sayantan Chattoraj – PhD Student (Sept. 2008-Nov. 2012)
Prof. Jiamei Chen – Visiting Scholar (Dec. 2015-Dec. 2016)
Dr. Miles Chen – Assistant Scientist (Apr. 2010-Dec. 2010)
Dr. Xingchu Gong – Visiting Scholar (Dec. 2013-Dec. 2014)
Prof. Xin He – Visiting Scholar (Feb. 2015-Feb. 2016)
Ms. Cosima Hirschberg – Visiting Scholar (May 2018-Sept. 2018)
Dr. Xiang Kou – Post-Doctoral Fellow (Aug. 2011-Nov. 2012)
Ms. Lili Liu – Visiting Scholar (Aug. 2015-Sept. 2016)
Mr. Sibo Liu – MS Student (Sept. 2017-July 2019)
Prof. Shuyu Liu – Visiting Scholar (Feb. 2016-Jan. 2017)
Dr. Benyong Lou – Visiting Scholar (Oct. 2013-Oct. 2014)
Dr. Frederick Osei-Yeboah – PhD Student (Sept. 2010-Sept. 2015)
Dr. Sarsvat Patel – Post-Doctoral Fellow (Apr. 2010-Aug. 2012)
Dr. Shubhajit Paul – Post-Doctoral Fellow (Jan. 2014-Mar. 2019)
Dr. Reddy Perumalla – Research Associate (Apr. 2010-Dec. 2015)
Dr. Limin Shi – Research Associate (Feb. 2009-Oct. 2014)
Mr. Zhongyang Shi – MS Student (Sept. 2017-July 2019)
Mr. Byoung-Hwa Son – Visiting Scientist (June 2010-June 2011)
Dr. Wei-Jhe Sun – PhD Student (Sept. 2012-Dec. 2017)
Mr. Majeed Ullah – Visiting PhD Student (Jan. 2014-July 2014)
Mr. Chenguang Wang – Visiting Scholar (June 2013-Sept. 2013, Dec. 2014-Oct. 2015)
Prof. Mingjun Wang – Visiting Scholar (Mar. 2016-Mar. 2017)
Prof. Wenxi Wang – Visiting Scholar (Mar. 2016-Mar. 2017)
Dr. Hiroyuki Yamashita – Research Scholar (Dec. 2015-Nov. 2016)
Ms. Hao Ye – Visiting Scientist (Aug. 2011-Nov. 2011)
Ms. Liang Zhengxuan – Visiting Scholar (Jan. 2018-June 2018)
Prof. Qun Zhou – Visiting Assoc. Research Professor (May 2011-May 2012)
Mr. Ling Zhu – MS Student (Sept. 2016-July 2019)

Instrumentation

Compaction simulator (the only unit in a pharmacy school in the U.S.)

Collecting fundamental physical parameters during tableting
Material sparing (1 – 5 g of powder)
Vast amount of information available, e.g., ejection force, take-off force, radial die-wall stress, compaction pressure-time profile, volume-time profile, tensile strength – pressure profile
Variable tableting speeds (capable of simulating most commercial tablet presses and roller compactors)
Flexible with tablet size and shape
Reliable prediction of success or failure during scale up

Ring shear cell

A well-established methodology
Predictive of powder flow property during powder transfer processes
Flow function, cohesion, and internal friction angle, bulk density
Superior to any other methods that assess flow property based on single point measurement
A large in-house flow database is available

Zwick universal material testing machine

A wide range of force (0.1 – 200 kN)
User-friendly software enabling study of relaxation and creep behavior
Controlled by force or displacement
Variable speed (0.01 - 100 mm/s)

Texture analyzer

High sensitivity (8 mN – 500 N)
Suitable for micro-indentation, film adhesion, mechanical properties of film, tablet tensile strength, breaking strength of granules

Nano-indenter

Suitable for studying mechanical properties of single crystals, films, and other small specimen
Exceptional sensitivity and spatial resolution

Other Instruments

Powder characterization

Helium pycnometer
Atomic force microscope (AFM)
Particle size analyzer
Scanning electron microscope (SEM)
Environmental SEM
X-Ray micro-tomography (micro-CT)
Zygo optical profilometer/Tencor stylus profilometer
Gas sorptometer (ASAP 2000)
Contact Angle Goniometer

Solid-state characterization

X-ray diffractometry (powder and single crystal) with temperature control
Moisture sorption apparatus
Thermo-gravimetry analyzer (TGA)
Differential scanning calorimeter (DSC)
Thermal mechanical analyzer (TMA)
Transmission electron microscope (TEM)
X-ray Photoelectron Spectroscopy (XPS)
Rotating disc dissolution rate apparatus (RDDR)
FTIR and Raman spectroscopy

Processing equipment

Lab scale spray-drier
Crystallizer (1 liter)
Lab-scale micronizer (Jet-mill)
PK blender
High shear granulator (1L, custom made; RotoLab, 1.8L)
Turbula mixer (Model T2F)
Comil (Model U5, underdriven)

Modeling

Materials Studio & Cambridge Crystal Database (supported by Minnesota Supercomputing Institute)

Collaboration Opportunities

We welcome opportunities to collaborate with industry on challenging projects. Some examples of such collaboration are listed below.

1. Assessing manufacturability of a formulation

a. Powder flow
b. Powder tabletability
c. Hygroscopicity
d. Drug release profile
e. Sticking tendency

2. Profiling solid-state properties of drugs and excipients

a. Polymorph screening and characterization
b. Salt screening
c. Cocrystal screening
d. Crystallinity
e. Crystal structure elucidation
f. Thermodynamic stability relationship
g. Process-induced crystal form conversion (trouble-shooting and control)
h. Drug-excipient compatibility

3. Profiling mechanical properties (crystal and powder)

a. Yield strength (in-die and out-of-die Heckel analysis)
b. Young’s modulus and tensile strength
c. Indentation hardness (nano- or micro-)
d. True density
e. Porosity of irregular specimens
f. Understanding tabletability, compressibility, compactibility, and elastic recovery, etc., under realistic manufacturing conditions
g. Mechanical behavior under high (GPa) pressures

4. Powder engineering (feasibility tests)

a. Formulation development
b. Process understanding (direct compression, dry and wet granulation)
c. Surface engineering for enhanced pharmaceutical properties

5. Instrument sharing

a. Easy access to state-of-the-art instruments
b. Cost savings on instrument maintenance and human resources
c. Ready access to expert guidance and training
d. Rapid turnaround time
e. High quality data