Application of In Vivo Imaging Techniques and Diagnostic Tools in Oral Drug Delivery Research

Abstract

Drug absorption following oral administration is determined by complex and dynamic interactions between gastrointestinal (GI) physiology, the drug, and its formulation. Since many of these interactions are not fully understood, the COST action on “Understanding Gastrointestinal Absorption-related Processes (UNGAP)” was initiated in 2017, with the aim to improve the current comprehension of intestinal drug absorption and foster future developments in this field. In this regard, in vivo techniques used for the characterization of human GI physiology and the intraluminal behavior of orally administered dosage forms in the GI tract are fundamental to gaining deeper mechanistic understanding of the interplay between human GI physiology and drug product performance. In this review, the potential applications, advantages, and limitations of the most important in vivo techniques relevant to oral biopharmaceutics are presented from the perspectives of different research fields.

Leveraging Physiologically Based Modelling to Provide Insights on the Absorption of Paliperidone Extended-Release Formulation under Fed and Fasting Conditions

“…It is important to consider that PAL is a low-solubility drug and that the colonic luminal fluid volume is low, i.e., it may be a rate-limiting factor for colonic absorption. Therefore, any factor that improves the solubilization of the drug, such as food intake, along with a higher colonic transit duration can increase oral bioavailability [ 13 ]. Another possible explanation is that the food effect can also be related to a difference in the release from the OROS formulation (and not necessarily solubilization).…”

“…As the food effect may be related mainly to an increase in the solubilization of the drug, or a different Weibull maximum release, potential in vitro approaches to mimic this effect can be explored, such as the use of specialized buffers that represent fasting and fed conditions in non-sink conditions to assess the solubilization effect. Therefore, the use of biorelevant dissolution testing could be more predictive of the in vivo scenario [ 11 , 12 , 13 , 14 ].…”

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review

“…In some cases, magnetically shielded rooms may be required, and it is only able to detect one single dipole. 15 By contrast, magnetic resonance imaging (MRI) has become an increasingly popular and powerful imaging tool used for visualization and study of pharmaceutical processes within the gastrointestinal tract. 26 MRI is able to acquire cross-sectional images of the body with excellent soft tissue contrast, in real time and with a large field of view.…”

“…A comprehensive understanding of the fate and behavior of drug delivery systems in the gastrointestinal tract was introduced in 1976 by Casey and in 1981 by Hardy and Wilson . Knowledge gained from gamma scintigraphy studies has assisted with dosage form optimization, and quantification of the effects of formulation variables such as density, viscosity and coating on the transit of oral drug formulations . Studies using gamma scintigraphy have furthermore investigated the complex relationship between dosage form and food .…”

“…However, it does not allow anatomic referencing and requires costly specialized equipment which is not generally available. In some cases, magnetically shielded rooms may be required, and it is only able to detect one single dipole …”