International Journal of Pharmaceutics 417 (2011) 216–226 Contents lists available at ScienceDirect International Journal of Pharmaceutics journa l h omepa g e: www.elsevier.com/locate/ijpharm In vivo imaging of drug delivery systems in the gastrointestinal tract Werner Weitschies a,∗ , Clive G. Wilson b a Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany b Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, Scotland, UK a r t i c l e i n f o Article history: Received 20 January 2011 Received in revised form 19 July 2011 Accepted 19 July 2011 Available online 26 July 2011 Keywords: In vivo imaging Drug delivery systems Gamma scintigraphy Magnetic marker monitoring Magnetic moment imaging Magnetic pill tracking AC biosusceptometry Magnetic resonance imaging a b s t r a c t An essential basis for the understanding of the complex interplay between oral drug delivery systems and gastrointestinal physiology is the ability to relate deposition of the dosage form to the plasma concentra- tion time profile. The pharmaceutical scientist requires an array of methods that provide information on formulation disposition without influencing the physiological process, commonly termed “non-invasive” imaging modalities. In this paper, a short historical view on the suitability of different imaging modalities for the investigation of the fate of drug delivery systems in the GI tract is given. The focus of the review is the presentation of currently mostly used methodologies scintigraphy, magnetic tracking techniques like magnetic marker monitoring (MMM), magnetic moment imaging (MMI), AC biosusceptometry (ACB) and magnetic resonance imaging and the discussion of their strengths and weaknesses. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Drug substances have to reach the desired therapeutic target and maintain the appropriate concentration for a defined time span in order to be effective. In addition, the specificity of this physicochemical association determines the safety profile for the drug. This prerequisite holds true for every kind of delivery system and every route of administration. Among the different possibili- ties of introduction, the oral route is the most familiar mode for the administration for pharmacologically active substances. On a first, and superficial view, this seems logical as the gastrointestinal tract is the natural route for the uptake of all essential substances with exception of oxygen; however, unlike macronutrients poten- tial drug substances are absorbed from the gastrointestinal tract to a variable extent since appropriate biochemical triggers are not stimulated. In the past, we tended to think of the gut as a simple muscular tube that responded strongly to acetylcholine; but we are now aware of many short and longer range afferent/efferent loops innervated by a staggeringly large range of neurotransmit- ters, some of which are possibly generated by digestion. Over the last two decades, we have appreciated that the gastrointestinal pro- cessing of food is a very complex process that is in part managed by the so-called “gut brain axis” which consists of about 30% of all nerve cells (Romijn et al., 2008). ∗ Corresponding author. Tel.: +49 3834 864813; fax: +49 3834 864813. E-mail address: werner.weitschies@uni-greifswald.de (W. Weitschies). Not every component of a meal is useful and some are harmful. With precise and ultra-sensitive analytical methodology, we are aware of naturally occurring “impurities” in meat and vegetables including platicisers from packaging, sexual hormones in meat or fish and of course, alkaloids in plant seeds which are toxic. Some of these enemies are new, some have been around for millennia. The human gut responded by selection of a defense line consist- ing of metabolic enzymes and efflux transport systems which can be traced through evolution and differs in species. In addition, the gut is host to symbiotic microbes that also have the capability to degrade xenobiotics (Sousa et al., 2008). As a consequence, the delivery of drug substances via the oral route is more challeng- ing than digestion of burgers and salad. In therapy, the problem is solved by using less convenient routes of administration as for example the direct delivery into the body via injection or infusion. The complexity of oral drug absorption is challenging and despite numerous attempts, a completely robust prediction of the rate and extent of the absorption of drug substances from the human gas- trointestinal tract is neither provided by in silico methods nor by recourse to animal models. Our knowledge of drug absorption and application of these prin- ciples to drug design has moved beyond the simpler applications of the pH-partition hypothesis, for example through application of Lipinski rules. The key issue is that the new drug candidates get bigger, with lower solubility and more chirality which generates problems in delivery. In practice, for many promising candidates, the lack of an appropriate mode of delivery is becoming a limiting factor. 0378-5173/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2011.07.031