Lipid-Based Drug Delivery Systems Community

REGISTRATION LINK:

https://science360.aaps.org/science360/2025/webinars/4183649/karunakar.sukuru.ivivc.reimagined.real-time.in-vitro.solutions.for.lipid-based.html?f=menu%3D24%2Ac_id%3D4183649%2Afeatured%3D19743%2Ashow_banner_in_top_panel%3D1

Part I: IVIVC Reimagined: Real-Time In Vitro Solutions for Lipid-Based Formulation Challenges:

Lipid-based formulations (LBFs) delivered in softgel dosage forms have become an established strategy to enhance solubility, absorption, and bioavailability of poorly water-soluble and poorly permeable drugs (BCS Class II-IV). More than 70 FDA-approved products demonstrate their utility across therapeutic areas, with immediate-release (IR) and modified-release (MR) softgels enabling delivery of complex molecules and improving patient compliance.

Developing LBF softgels offers exciting opportunities for innovation, though it requires careful attention to factors such as capsule cross-linking (use of non-gelatin shell may be an option) and excipient consistency. By proactively addressing these variables and incorporating tailored study designs and predictive models, teams can ensure reliable dissolution and robust bioequivalence—even in the presence of food effects.

Current regulatory guidance often treats LBFs like conventional formulations, despite their digestion dependence and distinct in vivo behavior, creating gaps in bioequivalence assessment. 

This presentation reviews case studies illustrating both the opportunities and hurdles of IR-MR LBF softgels. It also highlights the need for physiologically based pharmacokinetic (PBPK) modeling, discriminatory dissolution testing, and risk-based regulatory approaches to advance the development of softgel LBFs for both innovator and generic applications. In addition, future areas of research focus to address the gaps in the current IVIVC guidance will be discussed.

Part II: Opportunities & Challenges with IR-MR Lipid Based Formulations (LBFs)

Establishing robust in vitro–in vivo correlation (IVIVC) for lipid-based drug delivery systems, especially SEDDS, remains a persistent challenge due to their complex dissolution and absorption dynamics. Traditional dissolution methods often fall short in predicting in- vivo performance, limiting their value for formulation optimization and regulatory acceptance. 

This presentation reimagines the IVIVC paradigm by introducing real-time, permeation-based in vitro tools—specifically the MacroFLUX system—that enables simultaneous dissolution and absorption analysis across a synthetic lipidic membrane. By closely mimicking gastrointestinal conditions, this approach delivers actionable, predictive insights that correlate strongly with in vivo pharmacokinetics, including AUC and Cmax.

Through case studies and formulation strategies, we will demonstrate how factors such as SEDDS composition, droplet size, and surfactant selection impact both in vitro and in vivo outcomes. By advancing beyond conventional dissolution, these real-time in vitro solutions empower formulation scientists and R&D leaders to overcome key challenges in lipid-based drug development, accelerating progress toward more predictable, bioavailable, and successful therapies.
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Jayachandra Ramapuram Ph.D., FAAPS
Professor of Pharmaceutics
Auburn University, Harrison College of Pharmacy
Auburn AL
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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