The NIPTE-FDA Excipients Database hosted at pharmaHUB Ann Christine Catlin Rosen Center for Advanced Computing Purdue University June 14, 2012

What is the vision for our database ? Establish a database that maintains values of fundamental pharmaceutical excipients material properties and contains models, methods, and best practices for using this data in the design of pharmaceutical products and processes.

Establish a database that maintains values of fundamental pharmaceutical excipients material properties and contains models, methods, and best practices for using this data in the design of pharmaceutical products and processes. An Excipients Database

Establish a database that maintains values of fundamental pharmaceutical excipients material properties and contains models, methods, and best practices for using this data in the design of pharmaceutical products and processes. with fully documented experiments

offering more than just data …. Establish a database that maintains values of fundamental pharmaceutical excipients material properties and contains models, methods, and best practices for using this data in the design of pharmaceutical products and processes.

Environment for collaboration database server web server training tools API process roller compactor Carr Index search tags databases content resources capture community knowledge and experience

Hosting the database at the Hub pharmaHUB: a cyber infrastructure developed at Purdue University to support collaboration among researchers, educational outreach, and the sharing of data, tools and resources for the pharmaceutical engineering community.

What is a Hub ? nanoHUB: an environment for scientific collaboration

Building a scientific community >220,000 users worldwide > 5,000,000 hits/month 25% of all.edu domains 116 classes at 76 institutions in users ran 350,000 simulations Selected as Purdue’s platform for online education

HUBzero-powered research communities Feb 2007: 1 hub Feb 2008: 5 hubs Feb 2009: 8 hubs Feb 2010: 21 hubs Feb 2012: 40 hubs All with their own funding streams, projects, developers hubzero.org

A Hub for pharmaceutical engineering  EVO seed funding from NSF, online since December 2007  pharmaHUB mission …  provide educational materials and experiences for training of pharmaceutical engineers & scientists  offer modeling, computational, and decision support tools for drug product & process design  support science and engineering research in pharmaceutical manufacturing  More than 62,000 visits in 2011… with 6000 core users, 900 organizations, 120 resources and 30 simulation tools  Ongoing funding: $1.9M NSF award to address complete product cycle development

Community shared resources

An example simulation tool

30 tools now availble ! Visualization of Molecular Crystals Particle-surface Adhesion Tablet Dissolution model Hopper Flow Discharge (Discrete Element Model) Rotating Drum (DEM) High Shear Mixer (DEM) NIR Spectra Analyzer Raman Spectral Analyzer Continuous Particle Blending (Compartment Model) Roller compactor: Steady State & Dynamic models Cake filtration model Guideline ontology & SWOOP ontology browser Multipurpose operation production planner (MOPP) Lyophilization Calculator …

Courses, modules and lectures Statistical Model Building and Design of Experiments Computational Methods for Molecular Crystals Visualization of Molecular Crystals Discrete Element Method (DEM) Characterization of Nanopharmaceutical Materials Colloids and Surfactants Liquid Mixing Fundamentals Sterilization and Disinfection Mixing Equipment and Processes API Process Unit Operations Development and Design Pharmaceutical Bulk Drug Production Application of ChE Principles to Drug Delivery Particle and Flow Characterization Introduction to Rheology of Complex Fluids Pharmaceutical concepts into introductory ChE courses …

100 modules now available

What are the benefits of a Hub ?  Purdue-supported hardware and grid-computing services  Constant support by the HUBzero Tech Team… with yearly upgrades and new technologies  Stable and well-funded cyber infrastructure with developments from other Hubs  Worldwide contributions  Ratings and reviews  Services to build and support Databases with worldwide access (and access control for special groups when needed)  Continuous upgrades for Database features !

Excipients Database Schema Excipients -MCC Products -Avicel PH 101 Lot # -P Properties -Particle Size Equipment -Malvern Mastersizer Test Method -Laser Diffraction Operator -Ting Wang

Excipients Database Structure Catalogs excipients, vendors, products, lots, test methods, equipment, properties Catalogs excipients, vendors, products, lots, test methods, equipment, properties Measurements raw data, chemical and test descriptions Measurements raw data, chemical and test descriptions Derivations & Plots of Measurements histograms, yield loci, powder flow function, frequency & cumulative distributions Derivations & Plots of Measurements histograms, yield loci, powder flow function, frequency & cumulative distributions Analysis Tools make decisions and solve problems Analysis Tools make decisions and solve problems Web Interface Web Interface

Database Support  Independent data collection from global community  User-friendly web-forms and spreadsheets  Input from academic institutions, industry & government  Cross-check for measurements obtained with different methods  Validation, ratings, reviews & feedback  Integrity of the data  Security of the Hub & database technology  Authentication, authorization  Tracking of the data collection  Audit of database activity logs  Usage statistics, patterns, trends (Google analytics)

Database exploration with “data views”  Unique, powerful & “feature-rich” exploration capability  Browse & search & sort  Export in spreadsheet format  Both raw and derived data  Link to images and documents  Link to drilldown “data views”  Automatic plots – line graphs, barcharts,  Statistical computations (e.g., least squares regression)  Access control/privacy with group-restricted data viewing

Excipients database collaboration

Database discussion forum

Database wish list

Sharing tool sessions

Knowledge for predicating the properties of the final product … the tablet Look up and compare chemical and physical properties critical to manufacturing, stability, and performance of drug products  Plot NIR spectra to explore property variations between vendors, between lots and even within lots  Use range searches on Hausner ratio and Carr index to identify flowability  Generate the shear cell powder flow function to determine if a powder is cohesive or free-flowing to help with sizing of hoppers  Evaluate tensile strength of compacts based on moisture content  Explore particle size, size variation and particle shape to understand cohesion, compressibility and shear strength

Excipient Database at pharmaHUB Demo! Steve Hoag, Carl Wassgren, Sudheera Fernando, Sumudinie Fernando, Ting Wang, Kristine Alston, Linus Mockus