2 3 4 5 6 Formulation design Manufacturing process design Virtual patient population (PBPK, PDPK)...
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- 6 Formulation design Manufacturing process design Virtual
patient population (PBPK, PDPK) API physical properties Dosage
parameters Target release profile Manufacturing parameters Dosage
regimen Patient population parameters Pharmacokinetic,
pharmacodynamic response prediction Target vs predicted API release
profile prediction Drug (API) Design modification logic
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- 9 ManufacturesGrades Particle Size, m Moisture, % Loose Bulk
Density, g/cc FMCAvicel PH101503.0-5.00.26-0.31 JRS Vivapur 101
65-- 0.26-0.31 Emcocel 50M0.25-0.37 AKC PH-101 502.0-6.0 0.22
UF-7110.21 KG-8020.12 KG-10000.29 FMCAvicel
PH-1021003.0-5.00.28-0.33 JRS Vivapur 102 100-- 0.28-0.33 Emcocel
90M0.25-0.37 AKCPH-102902.0-6.00.30 FMC = FMC BIOPOLYMERS AKC =
Asahi Kasei Corporation JRS = J Rettenmaier & Shne GmbH and
Co.KG
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- 10 40 data points from 9 sources E 0 : mean = 7.1 GPa stdev =
1.9 GPa rsd = 0.27 Variation due to natural variation, testing
method, other? Need standardized, trustworthy source of data.
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- 11 Excipients - MCC Products - PH101 Lots - Lot # 1 Properties
- particle size Test method - Light scattering Equipment - Malvern
USP compendial category Actual product on the market
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- 12 Catalog of properties and measurements Raw data, chemical
& test descriptions Measurement presentation of data Derived
from raw data e.g., particle size, histogram Tools for usage e.g.,
how to ID excipients to solve problems User Interface
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- 19 2 components 9% active 2 components 30% active 3 components
9% active, 2% additive
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- 20 Void Structure
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- 22 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 X-ray CT
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- 24 Tablet represented on Cartesian grid Each cell is assigned:
o Number and size of particles o Active particle dissolution
coefficient o Solvent penetration coefficient o 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 o Uniform
o Density based o Fluid-Shear influenced Simple depiction of
solvent penetration over defined grid Pharmahub input gui for
tablet dissolution
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