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
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Introductions
Database overview
PharmHub overview & database demonstration
Test methods overview
Feedback summary
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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
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Key issues
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Measurement variability sources
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Trying to account for
in database
Excipient variability
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Method differences
Technique differences
Test conditions
Within supplier
Between suppliers
Critical Quality Attributes (CQA) not always known
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E.g., degree of substitution of HPMC
– Surface area of Mg Stearate
– Unknown factors
Trying to catalog
in database
Development Strategy
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Won’t solve problem of excipient
functionality with one project
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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
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Current properties
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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
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Handbook of excipients
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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
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Angle of repose
Density (bulk, tapped and true)
Flowability
Melting point
Moisture content
NIR spectra
Particle size distribution
Solubility
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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.
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With PharmHub we can:
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Create online community of users to share
information
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Capture information in real time
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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
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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
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Worked with individuals and organizations
for database guidance
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IPEC
Pharm IQ
Knowledgeable individuals in Pharma
Database sustainability
Presentation Style
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We would like this to be interactive
discussion not a lecture
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Please feel free to interrupt at any time!!!
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Can you…
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What would happen if….
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Can you show me….