Title: Plan for Approach to the Understanding and Predicting Excipient Properties and Functionality NIPTE - National Institute of Pharmaceutical Technology and Education Excipient Database Development Project August 15, 2011 update Today’s Agenda Introductions Database overview PharmHub overview & database demonstration Test methods overview Feedback summary – – Wish list for features Future steps NIPTE Participants NIPTE Personnel Affiliation Role Stephen W. Hoag Ting Wang University of Maryland, Baltimore School of Pharmacy PI Data collection Data modeling Carl Wassgren Kristine Alston Purdue University Dept. of Mechanical Engineering Data collection Data modeling Ann Christine Catlin Purdue University Sumudinie Fernando Rosen Center for Advanced Sudheera R. Fernando Computing Database technology and development Hub Cyber Infrastructure Linas Mockus NIPTE/Purdue Database data entry development Prabir Basu NIPTE Director of NIPTE Administrative Raw Material Inputs → CQA Excipient Properties •Crystal form •Particle size •Bulk density •Etc. Relationships Not well understood Critical Quality Attributes •Hardness •Disintegration time •Dissolution •CU/mixing Excipient Variability Design Space Inputs Materials API Excipients Inputs Process Parameters Process Step Product (or Intermediate) Process Variability Product Variability Unforeseen/unknown excipient variability at the heart of many surprise product failures during production Excipient Characterization Key issues – Measurement variability sources – Trying to account for in database Excipient variability – Method differences Technique differences Test conditions Within supplier Between suppliers Critical Quality Attributes (CQA) not always known E.g., degree of substitution of HPMC – Surface area of Mg Stearate – Unknown factors Trying to catalog in database Development Strategy Won’t solve problem of excipient functionality with one project – Thus, focus on first step which is material properties of excipients Goal to develop database infrastructure with finite resources Start with DC and will expand to other categories as database grows – Current properties Chemical Description Flow Compactability Comparison of different grades of MCC Increase stability of moisture-sensitive drugs Increase flow 180 um PH-200 Particle size 150 um 100 um PH-102 SCG PH-302 PH-112 50 um PH-102 PH-113 PH-103 20 um NMT= not more than PH-301 PH-101 Increase batch size PH-105 NMT 1.5% FMC Loose bulk density NMT 2% NMT 3% Decrease moisture content 0.4g/cc NMT 5% 0.3g/cc Comparison of different grades from different manufacturers--MCC FMC = FMC BIOPOLYMERS JRS = J Rettenmaier & Söhne GmbH and Co.KG AKC = Asahi Kasei Corporation Manufactures Grades Particle Size, µm Moisture, % Loose Bulk Density, g/cc FMC Avicel PH101 50 3.0-5.0 0.26-0.31 JRS Vivapur 101 Emcocel 50M 65 -- PH-101 AKC UF-711 KG-802 JRS AKC Avicel PH-102 Vivapur 102 Emcocel 90M PH-102 0.25-0.37 0.22 50 2.0-6.0 KG-1000 FMC 0.26-0.31 0.21 0.12 0.29 100 3.0-5.0 100 -- 90 2.0-6.0 0.28-0.33 0.28-0.33 0.25-0.37 0.30 Database Structure Excipients - MCC ← USP compendial category Products - PH101 ← Actual product on the market Lots - Lot # 1 Properties - particle size Equipment - Malvern Test method - Light scattering Handbook of Excipients Handbook of excipients – – – – – – – – – – 1. Nonproprietary Names 2. Synonyms 3. Chemical Name and CAS Registry Number 4. Empirical Formula and Molecular Weight 5. Structural Formula 6. Functional Category 7. Applications in Pharmaceutical Formulation or Technology 8. Description 9. Pharmacopeial Specifications 10. Typical Properties Angle of repose Density (bulk, tapped and true) Flowability Melting point Moisture content NIR spectra Particle size distribution Solubility – – – – – – – – – 11. Stability and Storage Conditions 12. Incompatibilities 13. Method of Manufacture 14. Safety 15. Handling Precautions 16. Regulatory Status 17. Related Substances 18. Comments 19. Specific References Database Structure •Tools for usage • Eg how to ID excipients to solve problems •Measurement presentation of data •Derived from raw data •Eg CI, particle size, histogram •Catalog of properties and measurements • Raw data, chemical & test descriptions User Interface Database Features Cont. With PharmHub we can: – Create online community of users to share information – Capture information in real time – i.e., gives us the ability to pool user excipient experiences and data Discussion boards, forums etc. Online lectures Become the and Facebook® of excipients? Have the capability to gather product info. directly from manufactures production in real time Blind information Can put producers and usurer information in blinded from in database Gives capability to correlate users and producer data, which is not done currently Database Partners Worked with individuals and organizations for database guidance – – – IPEC Pharm IQ Knowledgeable individuals in Pharma Database sustainability Presentation Style We would like this to be interactive discussion not a lecture – Please feel free to interrupt at any time!!! Can you… What would happen if…. Can you show me….