Amorphous Materials: Theory and Practice in Pharmaceuticals and Devices Workshop

Thursday, January 16, 2014
University of MN, Twin Cities East Bank Campus

This IPrime Mid-Year Workshop will offer internationally recognized leaders discussing the properties of amorphous materials above and below the glass transition temperature. Large molecules such as polymers, small molecules such as drugs, and combinations of the two will be covered. Bulk and interfacial properties of amorphous materials and solid amorphous dispersions will be emphasized, and the impact of these properties on industrial processes and product performance will be considered.

Thursday, January 16, 2014
9:00 AM - 3:00 PM, check-in begins 8:30 AM
Jackson Hall, room 2-137 (2nd floor, bldg west side)
University of MN, Twin Cities East Bank Campus

Directions and Parking: Road construction is underway at the University. When planning your visit, please review campus building and parking locations and allow for extra travel time. (PDF Map)

This IPrime Mid-Year Workshop is presented by the Biomaterials and Pharmaceutical Materials (BPM) and Microstructured Polymers (MP) programs. Coordinators: BPM Program Leader Ron Siegel, BPM Faculty Raj "Sury" Suryanarayanan, and MP Program Leader Marc Hillmyer. Registration is required.

Description
In this workshop, internationally recognized leaders discussing the properties of amorphous materials above and below the glass transition temperature. Large molecules such as polymers, small molecules such as drugs, and combinations of the two will be covered. Bulk and interfacial properties of amorphous materials and solid amorphous dispersions will be emphasized, and the impact of these properties on industrial processes and product performance will be considered.

To Attend 
Register here by Friday, January 10. This workshop is free and open to IPrime member companies, invited guests, and University of Minnesota faculty, students, and staff. Prospective IPrime members interested in attending an IPrime event as a guest should contact Bob Lewis, ph: 612-625-1269.

Workshop Schedule
8:30 AM  Check-in begins (light breakfast served)

9:00 AM  Welcome and Introductions
Ron Siegel, University of Minnesota, BPM Program Leader

9:10 AM  Aging and Stability in Glass-Forming Liquids: From                Normal Aging to Ultrastable 20 Million Year Old Amber
Gregory McKenna, Texas Tech University
Abstract:: Physical aging of glassy materials has provided a means to address certain aspects of the temperature dependence of their dynamics, especially as it pertains to the so-called super-Arrhenius behavior as the glass temperature Tg is traversed. Here we look at the processes of physical aging in polymeric materials and how their understanding can lead to unique experiments that allow us to address the question of super-Arrhenius behavior, or the Vogel-Fulcher divergence of relaxation times or viscosities. In particular, we examine results from mechanical tests on polycarbonate that were the first to suggest that time scales actually do not diverge. We also look at dielectric data for a poly(vinyl acetate) material that shows the same sort of behavior. We terminate the aging discussion by showing novel experiments using a 20 million year old Dominican amber material that has an extremely low fictive temperature Tf relative to its Tg and that confirm the results for the other materials. Finally, we terminate with a brief discussion of the vitrification and crystallization of a poor glass-former, TNT, by showing the first data of its glass transition temperature and we show that the cooling rate for this crystallizable material has an important effect on the actual crystallization process that occurs after devitrification.

10:00 AM  Morning break (refreshments served)

10:30 AM Enhancing the Supersaturation of Crystalline
Hydrophobic Drugs with Modified Hydroxypropyl
Methyl Cellulose
Marc Hillmyer, University of Minnesota, MP Program Leader
Abstract: Novel hydroxypropyl methylcellulose (HPMC) esters were evaluated for their performance in improving the aqueous solubility of crystalline hydrophobic drugs in spray-dried dispersions (SDDs). We prepared five HPMC esters from a single HMPC precursor with varying structure and substitution levels. SDDs with different matrices at 10 wt% loading of the model drug phenytoin had very similar bulk properties. In aqueous suspensions, the SDDs of several HPMC esters not only allowed for the attainment of high initial supersaturation of phenytoin, but also maintained high concentrations for extended time. Such maintenance was ascribed to the inhibition of crystal nucleation. Structure-property relationships for these systems were developed and will be presented.

11:00 AM Diffusion in Molecular Glass Formers
Mark Ediger, University of Wisconsin
Outline: Self-diffusion in supercooled liquids - Tracer diffusion in supercooled liquids - Link between diffusion and crystal growth rates - Fast diffusion at glass surfaces -Stable glass formation via highly mobile surfaces - Influence of glass structure on water diffusion and uptake

11:50 AM  Lunch & Panel Discussion (box lunch provided for members)

1:00 PM  Challenges and Successes in Materials Characterization
using Positron Annihilation Spectroscopy
David Van Horn, University of Missouri, Kansas City
Abstract: After a brief introduction to positron annihilation lifetime spectroscopic techniques, results from three projects will be presented. First, films of different aircraft primer coatings are compared and contrasted in bulk and depth profile PALS analyses. Second, shear-strained polymers (PC and PMMA) are compared as a function of high pressure (to 140 MPa) to characterize their free-volumes and performance. Finally, some initial results from the characterization of modified titanium will be presented, with discussion related to its interface in biological systems. To conclude, the challenges of relating PALS to physical phenomena will be considered.

1:50 PM  Hydrogen Bonding and Molecular Mobility: Predictors of                Crystallization from the Amorphous State
Vishard Ragoonanan, University of Minnesota
Abstract: Solid dispersions which are molecular mixtures of a drug and polymer have shown great promise in the physical stabilization of amorphous drug compounds. However, their limited commercial success is attributed to the insufficient understanding of the fundamental mechanisms of physical stabilization of drugs by polymers. Both molecular mobility and hydrogen bonding interactions have been implicated in the physical stability of amorphous solid dispersions. Here we investigate the role of both, using dielectric spectroscopy and FTIR spectroscopy to monitor molecular motions and drug-polymer hydrogen bonding interactions, respectively. Our results suggest that crystallization is better coupled with rotational mobility in the glassy state than in the supercooled liquid state. We also observed that relaxation times were positively correlated with the extent of drug-polymer hydrogen bonding interactions. Physical stability and polymer selection will be discussed in light of these two results.

2:10 PM  Spray Dried Dispersions with Glycopolymers for Oral                Drug Delivery
Theresa Reineke, University of Minnesota

2:40 PM  Brief Panel Discussion & Concluding Remarks