Gastrointestinal Tracking and Gastric Emptying of Coated Capsules in Rats with or without Sedation Using CT imaging.

Noemí Gómez-Lado,Alvaro Goyanes,Christine M Madla,Vipul Yadav,Silvia Matiz,Abdul W Basit,Iria Seoane-Viaño,Pablo Aguiar

doi:10.3390/pharmaceutics12010081

Abstract

Following oral administration, gastric emptying is often a rate-limiting step in the absorption of drugs and is dependent on both physiological and pharmaceutical factors. To guide translation into humans, small animal imaging during pre-clinical studies has been increasingly used to localise the gastrointestinal transit of solid dosage forms. In contrast to humans, however, anaesthesia is usually required for effective imaging in animals which may have unintended effects on intestinal physiology. This study evaluated the effect of anaesthesia and capsule size on the gastric emptying rate of coated capsules in rats. Computed tomography (CT) imaging was used to track and locate the capsules through the gastrointestinal tract. Two commercial gelatine mini-capsules (size 9 and 9h) were filled with barium sulphate (contrast agent) and coated using Eudragit L. Under the effect of anaesthesia, none of the capsules emptied from the stomach. In non-anaesthetised rats, most of the size 9 capsules did not empty from the stomach, whereas the majority of the smaller size 9h capsules successfully emptied from the stomach and moved into the intestine. This study demonstrates that even with capsules designed to empty from the stomach in rats, the gastric emptying of such solid oral dosage forms is not guaranteed. In addition, the use of anaesthesia was found to abolish gastric emptying of both capsule sizes. The work herein further highlights the utility of CT imaging for the effective visualisation and location of solid dosage forms in the intestinal tract of rats without the use of anaesthesia.

Highlights

The use of animals in biomedical and pharmaceutical research remains essential to understand the mechanisms underlying disease pathology, as well as to contribute to the discovery of improved methods to prevent, diagnose and treat them [1]
Among the different animals used in preclinical research, rodents make up approximately 95% of all laboratory animals [2]
The aim of this study was to evaluate the influence of (i) capsule size and (ii) anaesthesia on the gastric emptying of size 9 and 9h capsules which are designed for oral administration to rats

Summary

Introduction

The use of animals in biomedical and pharmaceutical research remains essential to understand the mechanisms underlying disease pathology, as well as to contribute to the discovery of improved methods to prevent, diagnose and treat them [1]. Animal testing has provided an important tool to guide the translation of formulations from pre-clinical studies to first-in-human (FIH) clinical trials. Rats are one of the most widely used small animal models for the assessment of new pharmaceutical entities during pre-clinical studies [3,4,5,6,7,8,9]. The oral route is the most preferred and convenient way to administer drugs which can either be formulated to act locally in the gastrointestinal (GI) tract or be absorbed to achieve a systemic effect [10]. If a modified release of the drug in lower regions of the GI tract is pursued, a coating is generally applied on the capsule surface [12,13]

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