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RET 2012 – Dry Powder Coating

Final Presentation – 8/2/12Marie Aloia – Bayonne High School Charles Muchira – Central High School Newark

With: John Mankarious and Mina ShnoudahMentors: Zhonghui Huang and Dr. James Scicolone

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Plan: Merge Projects 4 and 8

•Project 4: Characterize the effects of coatings on the main components of pharmaceutical blends▫Properties: Flowability and Packing ▫Comprehensive testing for one API loading set of

blends – to compare to other API loading blends

•Project 8: Create a database of uncoated and coated powders that can be used to develop a predictive model to describe bulk properties.

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RET Project Summary•Project Parameters

▫Build Blends Database: Project 4 60% API- M-APAP, main Excipients (17% Lactose 450,

17% Avicel 105) 9 combinations of coated vs. uncoated, with M5P silica Characterization method: FT4

Bulk Density, Shear, and Compressibility Dissolution tests (future work)

▫Build single powder bulk density database: Project 8 10 powders, 6 coatings + AR = 70 samples Characterization method: FT4 and Rodos Models: Single/Multi asperity models

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What is Dry Coating? Why do we do it? What it is: • Dry coating places a nano-sized particle coating onto a

micro-sized particle• Several methods have been developed for doing this

Why we do it: • Pharmaceutical powders have very small particle sizes,

about 1-250µm • Particles in this size range are very difficult to handle

because of strong interparticle forces • Dry coating method diminishes the interparticle forces and

makes the pharmaceutical powder easier to handle.

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Project 4

Characterization of Surface Modified Pharmaceutical Blends

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Blends Database60% API M-APAP, 17% Lactose 450, 17% Avicel 105Balance: 5% Crospovidone + 1% Magnesium Stearate

1. All uncoated2. All uncoated – silica M5P, added3. Coated Lactose 4504. Coated Avicel 1055. Coated Lactose 450 + Avicel 1056. Coated API – M-APAP7. Coated M-APAP + Lactose 4508. Coated M-APAP + Avicel 1059. All coated

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Blends SystemmAPAP

+Avicel 105

+Lactose 450

V-blender

312.5rAdd MgSt

V-blender

31.25rBlends

Component  d 10 (µm) d 50 (µm) d 90 (µm) Span

Micronized Acetaminophen 2.3 11.1 40.8 3.5

Avicel PH105 7.2 19.7 43.5 1.9

Pharmatose 450 3.6 20.2 51.5 2.4

Crospovidone Kollidon-CL 16.2 75.2 214.2 2.6

Magnesium stearate - 4.2 -

Silica M5P - 0.02 -

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Blend Database Model – Bulk Density

0.35

0.4

0.450000000000001

0.500000000000001

0.55000000000000160%API

Bul

k D

ensi

ty (g

/ml)

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Blend Database Model – FFC

unco

ated e

veryt

hing

add s

ilica s

epar

ately

Coated L

actose

450

Coated Avic

el 105

Coated two ex

cipients

Coated API

Coated A

PI and c

oated L

actose

450

Coated A

PI and c

oated A

vicel 1

05

Coated e

veryt

hing0

2

4

6

8

10

12

60%API

FFC

FFC: 0-2 very cohesive; 2-4 cohesive; 4-10 Easy flowing; >10 Free flowing

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Blend Database Model Bulk Density vs FFC

0.35 0.4 0.45 0.5 0.550

2

4

6

8

10

12Phase Map

uncoated everything

Add silica separately

Coated Lactose 450

Coated Avicel 105

Coated two excipients

Coated API

Coated (API and Lac-tose450)

Coated (API and Avicel 105)

Coated everything

Bulk Density (g/ml)

FFC

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Compressibility

0 2 4 6 8 10 12 14 160

5

10

15

20

25

30

35

4060% API Blend

NoneNone- Silica AddedLactose450Avicel 105Lactose450+Avicel105API: M-APAPAPI+Lactose450API+Avicel105All

Applied Normal Stress, kinematic, kPa

Com

pres

sibi

lity

Perc

enta

ge%

Coated with M5P

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Project 8

Predicting the Bulk Density of Dry Coated Powders

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Single Powder Bulk Density Database70 Powder Samples

Coated by LabRam 75Gs 5MinParticle sizes measured with Rodos

10 powders 1. M-APAP2. C-APAP3. IBu504. IBu905. Potato starch6. Ascorbic Acid7. Granulac 2308. Sorbolac 4009. Pharmatose DCL1110. Aluminum

6 Coatings + AR1. M5P2. R972P3. TS5304. OX505. Alumina (Al2O3)6. TiO2 7. no coating (AR)

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Particle size informationGuest H2O * Size(nm)

M5P Yes 20

R972P No 16

TS530 Yes 7

OX50 Yes 40

Alumina Yes 13

TiO2 Yes 21

* Hydrophilic

Host D50 Size (µm)

M-APAP 11.07 C-APAP 25.40 IBu50 72.22 IBu90 129.50 Potato Starch 35.84 Ascorbic Acid 223.25 Granulac 230 22.09 Sorbolac 400 15.06 Pharmatose DCL11

126.16

Aluminum 50.32

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Single Powder Bulk Density DatabaseSample comparison of the effect of coating on Bulk density

1 2 3 4 5 6 70.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

AR

M5PR972P

TS530

OX50

Alumina TiO2

Bulk Density change for M-APAP

Ave

rage

Bul

k D

ensi

ty g

/mL

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What it looks like - M5P on M-APAP

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Modeling particle contactThree possible interactions

•Host – Host contact

•Guest – Host contact

•Guest – Guest contact

Single- Asperity Multi-Asperity

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Modeling Bulk DensityTwo models: Single and Multi Asperity • To obtain Bond Number

•To correlate with Porosity▫Porosity = 1 – (bulk density / particle density)

gD

FFFBo ad

gravity

ad

3

6

Force of Adhesion

Acceleration of gravity

Host particle diameterParticle Density

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Modeling Bulk DensityTwo models: Single and Multi Asperity •Calculate Fad to obtain Bond number•Single Asperity

▫Host – Guest model for single particle

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20 )2/1(12 zd

DDd

dDzAFad

Fad = Force of adhesion A = Hamaker Constant – material propertyd = Guest particle diameter D = Host particle diameterzo = Molecular distance – material property

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Modeling Bulk Density

0.1 1 10 100 1000 100000.4

0.45

0.5

0.55

0.6

0.65

0.7

0.75 Single Asperity Model

Bond Number

Poro

sity

Open Square = Ascorbic AcidBar = IBu50 Diamond = Sorbolac400Closed Square = Granulac230

M5P OX50R972P AluminaTS530 TiO2

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Modeling Bulk DensityMulti Asperity Model•Guest - Host

•Guest-Guest

• Bond Number

•Correlate with Porosity

222 204 1.2124 1 1

adAd AFz d d D

D SAC D

22 2 20 0 00 0

312 8 24(2 )2 /

adA dd D Ad ADFz d d z d zL z

gD

FFFBo ad

gravity

ad

3

6

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What will happen in my classroom?Marie Aloia – Bayonne High School Take away from RET: •Fluidized fine powders behave like any state of matter. •Fluid-solids behavior can be modeled

▫Advanced students will help build a table top fluidizer▫Intro to Engineering students will:

Create a calibration model for fluidizing solids Measure parameters, e.g. air flow rate and density change

to characterize a material, such as sand, potting soil or coffee beans

Use the model to predict behavior of other substances. Explore industry applications for solids fluidization

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What do I intend for Physics/I.E.D students after my RET Experience – Charles Muchira• Students will investigate static and kinetic friction concepts

by creating and developing an experimental set-up.• Students will use powder-like and cereal-like materials to

conduct and validate the results of their experiments showing the repeatability of their set-ups.

• Students will design and create the experimental set-up components using Autodesk design software (Inventor-v.12)

• Students will design and reverse-engineer the drop door mechanism of the Flodex apparatus and the experimental components that they designed for the friction experiments.

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Thanks to: Pre-College Programs • Dr. Howard Kimmel • Levelle Burr-Alexander • Dr. Linda Hirsch • Dr. Albert Narh

York Center for Particulate Engineering Lab• Dr. Rajesh Dave, Dr. James Scicolone,

and Dr. Ecevit Bilgili ▫Maxx Capece ▫Amanda Guertin (2012–REU)▫And especially to Zhonghui Huang for all her help

• Financial support by NSF (Award: EEC 908889)

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Back up slide: dry coating schematic process

Yuhua Chen, Jun Yang, Rajesh N. Dave, and Robert Pfeffer. Fluidization of Coated Group C Powders. AIChE (2008): 104-121.