pharmahub Collaboration for Pharmaceutical Engineering and Science Linas Mockus Ann Christine Catlin Purdue University

Transcription

1 pharmahub Collaboration for Pharmaceutical Engineering and Science Linas Mockus Ann Christine Catlin Purdue University

2 What is pharmahub? 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.

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

4 A Hub for pharmaceutical engineering 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

5 Outreach Sharing of R&D and educational output of national projects NSF ERC Structured Organic Particulate Systems National Institute for Pharmaceutical Technology & Education

6 Unit cells, labels View range Representation Options Wire frame Covalent Corey-Pauling-Koltun Van der Waals Contacts and Interactions Hydrogen bonds Crystal Graph Growth Units View Options Lighting, Perspective, Depth Visualization of Crystal Structure

7 Simulation of particle adhesion

8 Tablet Dissolution Process Environment - Performance X-ray CT Density variations in a tablet due to processing conditions (friction). PROCESS Flow around tablet (2-D approx.) ENVIRONMENT Simulation of erosion and dissolution considering the heterogeneous density distribution + Effects of FLOW Drug Release profile PERFORMANCE

9 Mechanistic Dissolution Model The dissolution tool simulates multiple processes simultaneously Track location of dosage/fluid interface and update boundary conditions Track progression of solvent absorption through excipient matrix Calculate API dissolution at particle level considering surface to volume ratio and current surrounding solvent concentration Model drug release as diffusion of drug solute out of excipient matrix

10 Tablet Model Tablet represented on Cartesian grid Each cell is assigned: Number and size of particles Active particle dissolution coefficient Solvent penetration coefficient Distance to nearest tablet surface Values assigned as simple concentrations radii and representative coefficients Tablet/Bulk fluid interface handled via level set Moving boundary conditions Erosion type can be Uniform Density based Fluid-Shear influenced Simple depiction of solvent penetration over defined grid Tool for tablet dissolution

11 The NIPTE-FDA Excipients Database hosted at pharmahub

12 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.

13 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.

14 with fully documented experiments 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.

15 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.

16 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

17 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

18 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

19 100 modules now available

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

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

22 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)

23 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

24 Excipients database collaboration

25 Database discussion forum

26 Database wish list

27 Sharing tool sessions

28 Excipient Database at pharmahub Thank you! Questions?