Research Articles
Scintigraphic Evaluation of a Novel Colon-Targeted Delivery System (CODES™) in Healthy Volunteers

https://doi.org/10.1002/jps.20063Get rights and content

Abstract

The purposes of this study are to investigate the gastrointestinal transit and release properties of a novel, colon-targeted delivery system (CODES™) administered to healthy volunteers using gamma scintigraphy and to confirm that lactulose functions to promote disintegration in the colon. Two placebo formulations were studied: one was CODES™, which consisted of a lactulose containing core overcoated with both Eudragit E and Eudragit L designed to rapidly disintegrate in the colon, the other was lactulose-free reference formulation (LFRF) that consisted of lactulose-free tablet core overcoated with the same materials. Transit and disintegration of the radiolabeled formulations were followed by gamma scintigraphy. In the fasted state, scintigraphic images indicated that CODES™ started to disintegrate in the ascending colon in the majority of subjects at 7.11 ± 2.01 h post-dose. Disintegration was complete within 1 h following commencement of in vivo release. In contrast, LFRF presented with prolonged in vivo disintegration properties. In the fed state, the disintegration period of CODES™ was almost comparable to that observed in the fasted state. Gamma scintigraphic studies clearly showed that CODES™ provides for rapid target site release in the colon regardless of the ingestion of food. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1287–1299, 2004

Section snippets

INTRODUCTION

Targeted delivery of drugs to the colon is considered a useful approach either in the treatment of local diseases such as inflammatory bowel disease,1 or the systemic absorption of proteins or peptides, which are degradable in the small intestine.2,3 Colon-specific drug delivery systems have been investigated and developed utilizing several approaches: timed release,4 by the change in pH,5 bacterial concentration,6 and pressure7 in the gastrointestinal (GI) tract.

A novel colon-targeted delivery

Dosage Form Preparation

Two kinds of formulations were prepared as shown in the Table 1. Both formulations contained radiolabelled Amberlite IRP-69 ion exchange resin (BDH, Poole, Dorset) with 111In (1 MBq/20 mg resin) in the tablet core. The CODES™ tablet core contained 200 mg of lactulose (Inalc, Milan, Italy). A lactulose-free tablet core was used to prepare a reference formulation. Magnesium stearate was obtained from Vat Chemicala B.V. (Rotterdam, Netherland). Polyvinylpyrrolidone (PLASDONE® K-29/32) was kindly

In Vitro Release Characteristics

The in vitro release data for the CODES™ and the LFRF are provided in Figure 2. In the JP first-fluid (pH 1.2) and the JP second-fluid (pH 6.8), both formulations showed no release for 4 h. Both formulations disintegrated and released when the dissolution medium was replaced with the Mcilvaine buffer solution (pH 5). These results suggested that when the pH around both formulations lowered, they could disintegrate and release immediately.

Gastrointestinal Transit

The transit data for the CODES™ and the LFRF following

CONCLUSIONS

The objective of this study was to investigate the GI transit and release properties of a novel colon-targeted delivery system, CODES™, administered in the fed and fasted state using gamma scintigraphy. Comparison of CODES™ with LFRF confirmed that the lactulose functions to promote disintegration in the colon. Delivery of CODES™ in the fed and fasted states allowed the affect of food to be assessed. Ingestion of food resulted in delayed gastric emptying times and ICJ arrival times for the

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