Thrust C: Structural Characterization and Modeling#top

 Understanding and predicting structure-property-function Relationships

The central objective of this Thrust is the development of the scientific understanding and quantification of the role of the structure on the observed function/performance for a particular class of materials: structured organic composites. In order to establish such a linkage between structure and function, we have identified the following goals:

1)      Develop and implement experimental techniques to survey the structural features of the composite systems. All techniques need to provide spatial resolution of the composites to reveal the internal structure. The scale of observation is dependent upon each system ranging from the molecular level to macroscopic level.

2)      Develop and implement mechanistic models to predict behavior (function) attendant to the internal structure of the composite system. These models need account for the critical features of underlying structure which are necessary to capture the dominant mechanisms associated with a given function.

3)      Develop and implement techniques to assess the performance of organic composites systems with emphasis on the capturing the evolution of the structure. In many cases, the measurable quantities represent indirect measures of the sought performance attributes, and thus, their relationships need also to be determined.

4)      Design experiments to assess the criticality of the assumed mechanisms as well as to establish measures for the degree of confidence of the developed models using both pre-established and ad-hoc techniques.

 

The accomplishment of these goals will provide a quantitative and mechanistic link between structure-function to predict the behavior of given structures and also the reverse link function-structure necessary for designing structures with a desired functionality. The path and connectivity between structure and function is schematically shown in Figure 2P-12.

 

Structures are ubiquitous in all materials systems from the subatomic to the macroscopic level. The key and central question is what feature at a given scale is persistent at the next level of observation. Current research efforts in this area which has resulted on a partial understanding for several material systems; leaving a more general answer as a grand and open challenge for the scientific community in the physical & chemical sciences. A derived challenge is to further quantify and model the impact of these persistent structural features in the observed response for enabling a systematic optimization of the structure for desired response. These relevant structural features should then be incorporated in the modeling approach. Within the material science and engineering community, methodologies that incorporate features at a given scale into the observed response at coarser scale are typical denoted as multiscale methods, where the central issues is how to effectively bride the length scales.

 

 

 

C. Strategic Plan and Thrust Connectivity for Thrust C

To develop the structure-function relationship, we have developed a coordinated plan where the main focus is on the material structure. The plan is composed of several complementary and interrelated efforts including: i) multiscale characterization the material structure, which will used as a database for the structural and multiscale models; ii) multiscale modeling based on the structures observed; iii) assessment of the material response attendant to its structure; iv) verification and validation of the models based on the ad-hoc experiments. The connectivity of these activities is schematically shown in Figure 2P-13, and thus the project activities naturally connect with projects in Thrusts A and B and provide information and models to Thrust D.

 

D. Key Scientific Deliverables for Thrust C

 1)     Improved understanding of microstructure formation and evolution in complex drug-polymer dispersions including the formation of lamellae structures due to eutectoid solidification.

2)     Improved understanding and quantification of the role structures on powder flow of heterogeneous mixtures, including short and long range segregation and agglomeration using a complementary experimental-computation approach.

3)     Multiscale models for predicting the mechanical behavior of granular solids including the evolution of strength during processing. The key issue is the integration of single-scale models. There are several challenges in this integration process, notably the identification of the features at the finer scale that have a persistent effect in the upper scale.

4)     Mechanistic models to predict the role of shear on the structure/porosity of consolidated materials.

5)     Experimental techniques to conduct multi-resolution characterization of defects on solid structures (porosity/cracks).

6)     Methodologies for spatially and chemically mapping structures solid systems including drug loaded polymeric films, tablets and multilayer dosages.

7)     Methodologies to assess and quantify the role of structures on drug release profiles.

 

The central objectives of the project will be coordinated with those of Thrust C to provide:

 Technological objectives (coordinated with test beds)

Faculty: Bo Michniak-Kohn (Lead) (Rutgers), Madeline Torres (UPRM), Rodolfo Pinal (Purdue), Alberto Cuitiño (Rutgers), Fernando Muzzio (Rutgers)

Mentors: Shadi Madieh (GSK), Oscar Liu (Schering Plough), David Sperry (Lilly), Shirlynn Chen (Boehringer Ingelheim), Richard Hsia (Sepracor)