The particle drifting effect in the context of drug delivery and absorption emphasizes the importance of nanosized colloidal particles in enhancing therapeutic efficacy. As these particles navigate through the gastrointestinal (GI) tract, they encounter various barriers, including the aqueous boundary layer that exists near the intestinal wall. This layer presents a diffusional resistance that can hinder the absorption of larger molecules and traditional drug formulations.
Mechanistic Understanding
Particle Size and Surface Properties: The size of the colloidal particles plays a critical role. Nanosized particles (typically under 100 nm) exhibit a high surface area-to-volume ratio, which can enhance solubility and interaction with the intestinal mucosa. Additionally, modifications to surface properties, such as charge and hydrophilicity, can influence how these particles interact with the boundary layer.
Diffusion Dynamics: Nanosized drug particles can effectively reduce the diffusional resistance encountered in the aqueous boundary layer. Their movement is governed by Brownian motion, which increases with decreasing particle size. This allows them to navigate through the viscous boundary layer more efficiently than larger particles.
Particle Drift Mechanism: Particle drifting effect can be attributed to various factors, such as hydrodynamic interactions and electrophoretic mobility. When subjected to fluid shear stresses in the GI tract, nanoparticles may drift towards the intestinal wall due to enhanced transport mechanisms, reducing the likelihood of aggregation and facilitating absorption.
Influence of GI Environment: The composition of the GI content, including bile salts, enzymes, and pH, can also affect the stability and behavior of nanoparticles. Understanding these interactions is key to optimizing particle design for enhanced absorption.
How do we make more accurate Particle Drift predictions?
Mathematical Modeling: Development of predictive models that incorporate factors like particle size, surface coatings, and environmental conditions can aid in simulating how particles interact with the boundary layer.
In Vitro and In Vivo Studies: Conducting systematic studies that mimic GI conditions can provide insights into the performance of nanosized drug formulations. Techniques such as dynamic light scattering (DLS) and microscopy can help visualize particle behavior in simulated biological environments, and in vitro flux experiments, such as those provided by Pion's flux systems and Predictor software, which can explain how modified small particles and colloids alter absorption rate and predict the in vivo absorption rate and effective permeability of drug compounds.
Future Direction
Continued research is needed to elucidate the complex interactions between nanosized colloidal particles and the intestinal environment. Collaboration between physicists, chemists, and pharmacologists will tap into innovative formulation strategies, aiming to enhance the clinical efficacy of drug delivery systems while ensuring safety and compliance with regulatory standards.
Pion’s Predictor Software applies the mechanisms of the Gastrointestinal Unified Theoretical (GUT) framework to convert in vitro flux data to predictions of in vivo oral absorption and percent fraction drug absorbed (Fa%). When you apply Predictor software to flux data collected by Pion’s Rainbow Dynamic Dissolution Monitoring system, the Predictor data can help you understand the interplay between dose (Do), dissolution (Dn,) and permeability (Pn) to help you understand where to target formulation improvements.
Predictor assigns an estimation of the rate-limiting step to absorption of the API based on the Do, Dn and Pn numbers calculated from the Fa% and defines whether the compound is subject to a permeability, dissolution, or solubility-permeability limitation.
Additionally, Predictor is able to classify the drug according to the Biopharmaceutics Classification System (BCS) based on the Do and Pn numbers determined from the Fa% result. Formulation scientists can then decide on a strategy for improving oral absorption outcome by overcoming the significant rate-limiting steps for their drug.
Contact us to learn more.
