Mechanistic PBPK Modeling of Rectal and Vaginal Drug Absorption

Advanced In Silico Predictions for Non-Oral Routes

The rectal and vaginal routes represent critical pathways in modern pharmaceutical development—yet they remain underexplored in many PBPK modeling programs. This on-demand workshop equips scientists, formulation experts, and regulatory professionals with the mechanistic knowledge and practical tools needed to predict systemic drug absorption and bioavailability for these specialized administration routes.

Who Should Enroll?

• Formulation scientists developing rectal suppositories, vaginal rings, or other non-oral products
• PBPK modelers and regulatory affairs professionals seeking specialized expertise in non-oral routes
• Clinical pharmacology and bioequivalence specialists supporting pediatric, women's health, or contraceptive programs
• Regulatory strategists building dossiers for rectal or vaginal product submissions
• Pharmaceutical scientists in women's health, sexual health, pediatrics, and orphan disease development
• Contract research organizations (CROs) offering PBPK consultancy for diverse administration routes

Who Needs This Knowledge?

Regulatory and Development Professionals working on:

• Pediatric formulations (rectal suppositories for fever, pain, and seizure management in children unable to swallow)
• Contraceptive and sexual health products (vaginal rings, gels, and microbicides with complex absorption profiles)
• Women's health therapeutics requiring vaginal delivery (hormonal therapies, antimicrobials, and long-acting formulations)
• Orphan and rare disease medications leveraging rectal delivery for systemic effect
• Drug-device combinations where formulation engineering directly impacts bioavailability

Strategic Business Value

• Rectal Route: Bypasses hepatic first-pass metabolism for certain compounds; enables systemic delivery in pediatric, geriatric, and critically ill populations with dysphagia or GI complications
• Vaginal Route: Offers rich vascularization, large surface area, and reduced enzymatic activity—enabling lower doses, improved tolerability, and extended-release formulations that command premium positioning
• Virtual Bioequivalence (VBE): PBPK-driven VBE strategies reduce costly in vivo bioequivalence studies for generic/follow-on vaginal formulations, accelerating time-to-market

Course Overview

Duration: 30-day access post-registration

Course Length: ~3 hours of video instruction + ~3 hours of hands-on Simcyp Simulator work

Total Expected Commitment: 6+ hours

What You'll Learn

This workshop provides a comprehensive, case-driven exploration of mechanistic absorption modeling for non-oral routes:

Rectal Absorption Module

• Detailed rectal physiology, histology, and implications for drug transport
• Classification of rectal drugs and formulation strategies (suppositories, solutions, foams, enemas)
• Mechanistic Rectal Absorption Model (MechRAM): structural assumptions, parameter definitions, and physiological inputs
• Practical parameterization techniques for leveraging in vitro dissolution, permeability, and metabolism data
• Real-world case study: Sodium Naproxen suppositories with sensitivity analysis on formulation attributes

Vaginal Absorption Module

• Vaginal physiology, hormonal cycle considerations, and microbicide/contraceptive perspectives
• Vaginal formulation diversity (rings, gels, creams, tablets) and their mechanistic drivers
• Mechanistic Vaginal Absorption Model (MechVAM): model structure, design assumptions, and validation approaches
• Parameter estimation and optimization workflows
• Three distinct case studies:

• Dapivirine gel and ring formulations (microbicide/PrEP applications)
• Etonogestrel and Ethinyl Estradiol rings (contraceptive formulations with complex pharmacokinetics)
• Clindamycin phosphate cream (topical antimicrobial with systemic absorption)

• Virtual Bioequivalence (VBE) for vaginal formulations: regulatory strategy, predictive modeling, and approval pathways

Hands-On Practice

Four guided workshops for each route allow you to:

• Familiarize yourself with model structure and inputs
• Execute initial simulations with real case data
• Optimize parameters based on in vitro and clinical information
• Evaluate formulation impacts on systemic exposure
• Apply learnings to regulatory submissions and development decisions

Course Structure & Access

Temporary License: A 2-day Simcyp Simulator license is provided with your registration—ideal for completing all practical exercises

Expert Support: One office hour with a senior Simcyp scientist (scheduled post-registration) to guide your learning and address specific questions

No Downloadable Materials: Lectures and slides remain accessible within the portal for 30 days, ensuring active engagement with the content (though you may take your own notes)

Single-Seat License: The course purchase is for one individual; sharing login credentials is prohibited. Additional seats must be purchased separately.

Accessing Your Course: After registration, log into your Dashboard to begin immediately. You'll have 30 days to work through videos and complete assignments.

Prerequisites

Participants should have foundational familiarity with the Simcyp Simulator platform and basic PBPK concepts (e.g., absorption, distribution, metabolism, clearance). Prior attendance at Certara's Simcyp Introduction course or equivalent hands-on experience is recommended.

Course Topics & Lectures

RECTAL ABSORPTION MODEL

1. Introduction – Clinical context and regulatory landscape
2. Rectal Physiology Fundamentals – Anatomy, blood flow, metabolism, and implications for drug transport
3. Rectal Drugs and Formulations – Suppositories, solutions, retention enemas, foams; formulation considerations
4. MechRAM Structure – Model assumptions, compartments, and physiological drivers
5. MechRAM Parametrization – Estimating input parameters from in vitro and clinical data
6. Model Outputs and Interpretation – Plasma concentration profiles, bioavailability predictions, and sensitivity analysis

Hands-On Workshops:

• Sodium Naproxen Suppository – Model familiarization
• Sodium Naproxen Suppository – Initial simulation setup and outputs
• Sodium Naproxen Suppository – Parameter optimization and sensitivity analysis
• Impact of in vitro drug release data on systemic exposure predictions

VAGINAL ABSORPTION MODEL

1. Introduction to MechVAM – Vaginal route significance in women's health and sexual health
2. Vaginal Physiology Fundamentals – Anatomy, tissue composition, blood flow, microbicide/hormone considerations
3. Vaginal Drugs and Formulations – Rings (contraceptive, long-acting), gels, creams, tablets; formulation science
4. MechVAM Model Structure – Compartmentalization, physiological assumptions, and formulation interactions
5. MechVAM Parametrization – Building predictive models from dissolution, permeability, and clinical data
6. Model Outputs and Interpretation – Plasma and local vaginal concentrations, bioequivalence predictions

Hands-On Workshops:

• Dapivirine Gel and Ring Formulations – Microbicide absorption and systemic exposure
• Etonogestrel and Ethinyl Estradiol Rings – Contraceptive formulation complexity
• Clindamycin Phosphate Cream – Topical antimicrobial with systemic absorption
• Virtual Bioequivalence for Vaginal Formulations – Regulatory strategy and case study

Next Steps

Register today to access this advanced workshop for 30 days. Upon registration:

• Log into your Dashboard to begin video modules immediately
• Review the course material at your own pace
• Contact Certara to request your temporary Simcyp license (allow up to 48 hours)
• Schedule your expert office hour to optimize your learning experience
• Complete hands-on assignments and earn your certificateYour Instructors

• This workshop is led by world-class scientists from Certara's Simcyp division, each bringing deep expertise in non-oral drug delivery and mechanistic modeling

Your Instructors

This workshop is led by world-class scientists from Certara's Simcyp division, each bringing deep expertise in non-oral drug delivery and mechanistic modeling