INSIGHT Screening for Synergistic Combinations of Penetration - - PowerPoint PPT Presentation

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INSIGHT Screening for Synergistic Combinations of Penetration - - PowerPoint PPT Presentation

Oct 03, 2023 585 likes •737 views

INSIGHT Screening for Synergistic Combinations of Penetration Enhancers By ThienKhanh Pham Mentor : Amit Jain Co-mentor : Pankaj Karande Faculty Advisor : Samir Mitragotri Funded by : Center for Disease Control (CDC) and Fqubed Overview Goals

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SLIDE 1

INSIGHT Screening for Synergistic Combinations of Penetration Enhancers

By

ThienKhanh Pham

Mentor: Amit Jain Co-mentor: Pankaj Karande Faculty Advisor: Samir Mitragotri Funded by: Center for Disease Control (CDC) and Fqubed

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SLIDE 2

Overview Goals

Transdermal Drug Delivery?

A route that delivers drug across the skin barrier

1. Offers painless and sustained administration of therapeutic molecules 2. Avoids hepatic first pass metabolism and gastrointestinal degradation 3. Increases patient compliance

Chemical Permeation Enhancers ? »

Chemicals that help to increase the permeability of skin and offer low or no irritation

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SLIDE 3

Objectives

  • Finds suitable

Synergistic Combinations Of Penetration Enhancers

(SCOPE) formulations

Chemical Permeation Enhancers (CPEs)

  • Ternary Enhancers
  • Uses IN-vitro Skin Impedance Guided High-Throughput

(INSIGHT) screening to determine skin permeability

  • application of HTS tool
  • Collect data and analyze Enhancement Ratio
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SLIDE 4

IN vitro Skin Impedance Guided High Throughput screening

Karande & Mitragotri, Pharmaceutical Research, 19(5), 2002

1st Gen: 500-1000 formulations per day

Karande, Jain & Mitragotri, Nature Biotechnology, 22(2), 2004

5-10 formulations per day

Donor Array Receiver Array Skin

~

Donor Skin Receiver

Franz Diffusion cell

Sampling Arm

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SLIDE 5

INSIGHT Screening of SCOPE formulations

Safety Assay

ER

#

10 20 30 40 50 60 70 5000 10000 15000 20000

INSIGHT

In Vitro Permeation

  • f Dummy molecule

Successful Formulation

Understanding

In Vivo Study

Library Generation

ER IP ER

Epiderm TM Candidate Drugs

MW

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SLIDE 6

10 20 30 40 50 60 500 1000 1500 2000

Experiment Index Conductivity Enhancement ratio (ER)

0 to 10 10 to 20 20 to 30 30 to 40 40 to 50 50 to 60

INSIGHT Screening of Ternary Formulations

Potency

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SLIDE 7

INSIGHT Screening of Ternary Formulations

10 20 30 40 50 60 500 1000 1500 2000

Experiment Index Conductivity Enhancement ratio (ER)

0 to 10 10 to 20 20 to 30 30 to 40 40 to 50 50 to 60

High Potency from INSIGHT screening are evaluated for Irritation Potential (IP)

Distribution of Ternary Formulations from INSIGHT Screening

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SLIDE 8

Predicting Ternary Formulation Behavior From Binary Data

5 10 15 20 25 30 35 15 35 55 75

Predicted Ternary Enhancement Ratio Experimental Ternary Enhancement Ratio

average

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SLIDE 9

Theory Equation: ERABC = ERAXA + ERBXB + ERCXC + ERABXAXB + ERBCXBXC+ ERACXAXC

ER: Enhancement Ratio X: Composition A, B, C: Chemical Enhancers

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SLIDE 10

Achievements

  • Found potent ternary enhancer

formulations

  • Generated Ternary Enhancer data to be

used for theoretical predictions

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SLIDE 11

Future Plans

  • High Enhancement Potential formulations will be

evaluated for Irritation Potential (IP)

  • Potent and safe formulations will be evaluated in vitro for

flux enhancement using candidate drug

  • Successful candidate formulations will be tested in vivo

for bioavailability and safety

  • Select safe and potent Enhancer Formulations and find

why they work so well with FTIR and DLS studies

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SLIDE 12

Acknowledgements

  • Department of Chemical Engineering, UCSB:

– Amit Jain (Mentor) – Pankaj Karande (Co-Mentor) – Samir Mitragotri (PI)

  • National Science Foundation
  • INSET Program
  • Center for Disease Control (CDC)
  • Fqubed
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SLIDE 13

No More Pain and Pills