INSIGHT Screening for Synergistic Combinations of Penetration - PowerPoint PPT Presentation

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 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

Objectives • Finds suitable S ynergistic C ombinations O f P enetration E nhancers (SCOPE) formulations C hemical P ermeation E nhancers (CPEs) - Ternary Enhancers • Uses IN -vitro S kin I mpedance G uided H igh- T hroughput (INSIGHT) screening to determine skin permeability - application of HTS tool • Collect data and analyze Enhancement Ratio

IN vitro S kin I mpedance G uided H igh T hroughput screening Donor Skin Sampling Arm Receiver Donor Array ~ 5-10 formulations per day Skin Franz Diffusion cell Receiver Array 1 st Gen: 500-1000 formulations per day Karande & Mitragotri, Pharmaceutical Research, 19 (5), 2002 Karande, Jain & Mitragotri, Nature Biotechnology, 22 (2), 2004

INSIGHT Screening of SCOPE formulations Successful Formulation INSIGHT Library Generation 70 60 50 Understanding 40 ER 30 20 In Vivo Study 10 0 0 5000 10000 15000 20000 # Candidate Drugs Epiderm TM ER ER MW In Vitro Permeation IP of Dummy molecule Safety Assay

INSIGHT Screening of Ternary Formulations Conductivity Enhancement ratio 60 50 0 to 10 40 10 to 20 20 to 30 (ER) 30 to 40 30 40 to 50 50 to 60 20 Potency 10 0 0 500 1000 1500 2000 Experiment Index

INSIGHT Screening of Ternary Formulations Distribution of Ternary 60 Conductivity Enhancement 50 Formulations from 0 to 10 40 ratio (ER) 10 to 20 20 to 30 30 to 40 30 40 to 50 50 to 60 INSIGHT Screening 20 10 0 0 500 1000 1500 2000 Experiment Index High Potency from INSIGHT screening are evaluated for Irritation Potential (IP)

Predicting Ternary Formulation Behavior From Binary Data 35 30 Experimental Ternary Enhancement Ratio 25 20 average 15 10 5 0 15 35 55 75 Predicted Ternary Enhancement Ratio

Theory Equation: ER ABC = ER A X A + ER B X B + ER C X C + ER AB X A X B + ER BC X B X C + ER AC X A X C ER: Enhancement Ratio X: Composition A, B, C: Chemical Enhancers

Achievements • Found potent ternary enhancer formulations • Generated Ternary Enhancer data to be used for theoretical predictions

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

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

No More Pain and Pills