Related Experiment Video
Updated: Jan 16, 2026
10:22
In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
26.7K
Exploring Experimental and Statistical Approaches to Control Oversensitivity of In Vitro Permeability to Excipient
Mauricio A García1, Alexis Aceituno2,3, Nicole B Díaz1
1Departamento de Farmacia, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
Pharmaceutics
|September 27, 2025
Summary
This study investigated excipient effects on drug permeability using cell monolayers. Minoxidil failed to control oversensitivity, but ANOVA analysis reduced it, though CI90 may suit specific formulation comparisons.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Biopharmaceutical Sciences
- Cellular Assays
Background:
- Static in vitro permeability assays using cell monolayers are standard for Biopharmaceutics Classification System (BCS) drug classification.
- These assays exhibit oversensitivity to excipient effects, limiting their use in formulation studies.
- Investigating methods to control this oversensitivity is crucial for accurate drug permeability assessment.
Purpose of the Study:
- To evaluate the impact of common pharmaceutical excipients on the permeability of model drugs across cell monolayers.
- To assess two statistical approaches, normalization by minoxidil permeability (nPR) and confidence intervals (CI90), for controlling assay oversensitivity.
- To compare the efficacy of ANOVA and CI90 in identifying excipient-mediated changes in drug permeability.
Main Methods:
- Drug permeability assessed across MDCK-wt cell monolayers with and without excipients.
- Minoxidil used as a high-permeability marker to normalize results (nPR).
- Excipient effects analyzed using ANOVA (p < 0.01) and 90% confidence intervals (CI90).
Main Results:
- Sodium lauryl sulfate, microcrystalline cellulose, and sodium starch glycolate were the most impactful excipients.
- Minoxidil normalization (nPR) unexpectedly increased, rather than decreased, the observed excipient effects.
- CI90 analysis identified more excipient effects (41) than ANOVA (32), but ANOVA better reduced overall oversensitivity.
Conclusions:
- Minoxidil is ineffective in controlling the oversensitivity of cell-based permeability assays to excipients.
- ANOVA demonstrates a superior ability to mitigate oversensitivity to excipient effects compared to CI90.
- CI90 analysis may offer value in specific scenarios, such as comparing the performance of two formulations on drug permeability.
Related Concept Videos
01:16Methods for Studying Drug Absorption: In vitro
574
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
574
01:17In Vitro Drug Dissolution: Alternative Methods
198
Alternative drug dissolution methods include the rotating bottle, intrinsic dissolution test, peristalsis, and the Franz diffusion cell method. The rotating bottle method involves meticulously rotating tightly capped controlled-release beads in a temperature-controlled bath. Periodic decanting of samples allows for residue assay, followed by refilling with fresh medium and testing at various pH levels to emulate the gastrointestinal tract conditions.In contrast, the intrinsic dissolution test...
198
01:13In Vitro Drug Dissolution: Compendial Testing Models I
230
Compendial dissolution methods are standardized procedures defined by pharmacopeias to evaluate the rate at which a drug dissolves in a specific medium. These methods ensure batch-to-batch consistency, enable quality control, and support the prediction of drug bioavailability. They are critical for both immediate and modified-release drug products.The apparatuses used for dissolution testing differ in their design and mechanical function, but all aim to simulate the physiological environment of...
230
01:09In Vitro Drug Dissolution: Compendial Testing Models II
257
Various dissolution methods are utilized to assess a drug’s dissolution rate, including the flow-through cell, paddle-over-disk, cylinder, and reciprocating disk methods.The flow-through cell apparatus (USP (United States Pharmacopeia) method 4) comprises a reservoir for the dissolution medium and a pump that propels the medium through the cell containing the test sample. This method is crucial for assessing modified-release dosage forms with minimally soluble active ingredients,...
257
01:10In Vitro Drug Release Testing: Overview, Development and Validation
310
In vitro dissolution and drug release tests assess how quickly and how much of a drug is released from its dosage form into an aqueous medium under standardized laboratory conditions. These tests are essential tools in pharmaceutical development and quality assurance, offering insight into the drug's performance before clinical use.During formulation development, dissolution testing identifies incomplete or inconsistent drug release issues. It also supports decisions on selecting the optimal...
310
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
407
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
407