A Multiscale Simulation Toolkit for Computational Pharmacology of Trans/Intradermally Administered Compounds in Healthy and Diseased Population

Response to National Institutes of Health Small Business Innovation ResearchSBIRPhase II Application for GrantRFDAFunding Opportunity TitleResponse to National Institutes of Health Small Business Innovation ResearchSBIRPhase II Proposal for the GrantRFDASolicitation Topic CodeFDA Phase I ContractRFDAAgencyHHS Agency Tracking NumberRFDProposal TitleA Multiscale Simulation Toolkit for Computational Pharmacology of Trans Intradermally Administered Compounds in Healthy and Diseased Population ABSTRACT Delivery of therapeutic drugs via the dermal route is a promising alternative to oral or parenteral delivery routes because dermal drug delivery systemsDSoffer unique advantages such as controlled drug release over sustained periods for steady absorption into the systemic circulationsignificant reduction in first pass effects and gastrointestinal irritationreduced dosing frequency and systemic toxicityand better patient complianceWhile less than twenty transdermal drugs have been approved in the U Ssincethe number of generic drugs has steadily grown over the last three decadesAdditionallythe market for intradermal delivery systems is also expandingAccordinglythe market potential ofDSvalued at$B inis expected to reach$B bywith an annual growth rate ofIn response to this trenda physiologically inspired simulation toolkit that can predict the clinical pharmacokinetic response and therapeutic effect of dermally administered compounds by optimizing dosageformulation and administration scenariose gregimentingcan complement and accelerate drug developmentclinical investigations and regulatory evaluationTo this endthe overall goal of this project is to develop and deliver a multiscale simulation toolkit for computational pharmacology of trans intradermally administered compoundsCPDACin healthy and diseased skin populationDuring Phase Iwe developed a model of healthy skin and linked it with a systems pharmacology model and predicted the dermal absorption and clinical pharmacokinetics of first generationGentransdermal systemspatchescreamsgels and ointmentsand validated with clinical dataGoing into Phase IIwe will augment the scope of CPDAC by including additional Gentransdermal systemssecond and third generationGenanddermal drug delivery systems in healthy and diseased skin populationSpecificallywe will developquantitative structure activity relationshipQSARbased generalized constructs to automate the action of chemical penetration enhancersCPEson drug permeationcomputational models of field assisted iontophoresisGenand microneedle based intradermal drug deliveryGenwhich have not been attempted beforeThe models will be designed in a modular parametric form to accommodate subjectspecific physiologyuser defined fidelities of specific skin layersDDembedded skin microvasculatureThe models will then be integrated into aholistic trans intradermal modelwhich will then be linked to an advanced in vitro to in vivo correlationIVIVClinked whole body physiologically based pharmacokinetic modelPharmaLab CTSfor predicting the local and systemic pharmacokinetics of drugsgenerics and cosmetics delivered from Gensystemsin healthy and diseased skin populatione gpsoriasiseczemaacne and keratosisIn collaboration with our preclinical and clinical partnersthe models will be systematically calibrated and validated at each stage of the development process toward delivering a robustpredictive and commercial quality CPDAC toolkit for end user evaluationas GUI to pharmaFDA and therapeutic product developersResponse to National Institutes of Health Small Business Innovation ResearchSBIRPhase II Application for GrantRFDAFunding Opportunity TitleResponse to National Institutes of Health Small Business Innovation ResearchSBIRPhase II Proposal for the ApplicationRFDASolicitation Topic CodeFDA Phase I ContractRFDAAgencyHHS Agency Tracking NumberRFDProposal TitleA Multiscale Simulation Toolkit for Computational Pharmacology of Trans Intradermally Administered Compounds in Healthy and Diseased Population NARRATIVE Delivery of therapeutic drugs via the dermal route is a promising alternative to oral or parenteral delivery routes because dermal drug delivery systemsDSoffer unique advantages such as controlled drug release over sustained periods for steady absorption into the systemic circulationsignificant reduction in first pass effects and gastrointestinal irritationreduced dosing frequency and systemic toxicityand better patient complianceWhile less than twenty transdermal drugs have been approved in the U Ssincethe number of generic drugs has steadily grown over the last three decadesAdditionallythe market for intradermal delivery systems is also expandingAccordinglythe market potential ofDSvalued at$B inis expected to reach$B byIn response to this trendwe will develop a physiologically inspired dermal simulation toolkit called CPDAC for predicting the clinical pharmacokinetic response and therapeutic effect of dermally administered compounds by optimizing dosageformulation and administration scenarios to complement and accelerate drug developmentclinical investigations and regulatory evaluation