Research ArticlesScintigraphic Evaluation of a Novel Colon-Targeted Delivery System (CODES™) in Healthy Volunteers
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
REFERENCES (23)
- et al.
Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting
Int J Pharm
(2000) - et al.
Liner type azo-containing polyurethane as drug-coating material for colon-specific delivery: Its properties, degradation behavior, and utilization for drug formulation
J Control Rel
(2000) - et al.
Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers
J Control Rel
(1998) - et al.
Studies on lactulose formulations for colon-specific drug delivery
Int J Pharm
(2002) - et al.
Colonic transit of different sized tablets in healthy subjects
J Cont Rel
(1993) - et al.
The effect of food on the gastrointestinal transit and systemic absorption of naproxen from a novel sustained release formulation
J Cont Rel
(1995) - et al.
A comparative study of the gastrointestinal transit of a pellet and tablet formulation
Int J Pharm
(1984) - et al.
Gastrointestinal transit of non-disintegrating tablets in fed subjects
Int J Pharm
(1989) - et al.
The effect of tablet size on the gastric emptying of non-disintegrating tablets
Int J Pharm
(1990) - et al.
Socioeconomic evaluations on drug treatment for inflammatory bowel disease (IBD)—effect of a controlled-release mesalazine tablet (N-5ASA)
Rinshoiyaku
(1995)
A new approach to the oral administration of insulin and other peptide drugs
Science
Cited by (60)
Efficient colonic drug delivery in domestic pigs employing a tablet formulation with dual control concept
2023, Journal of Controlled ReleaseClinical translation of advanced colonic drug delivery technologies
2022, Advanced Drug Delivery ReviewsCitation Excerpt :Once in the colon, the lactulose component of the tablet begins to be fermented by bacteria. SCFAs produced during fermentation induces the dissolution of the acid-soluble Eudragit® E coating, exposing the tablet core and prompting drug release [246,247]. Whilst sequential triggering systems combine more than one mechanism, in reality, they do not actually circumnavigate the risk of drug release failure nor provide a significant improvement in the reliability of the formulations.
Interspecies differences in gastrointestinal physiology affecting the in vivo performance of oral pharmaceutical solid dosage forms
2022, Journal of Drug Delivery Science and TechnologyCitation Excerpt :Another example of an oral drug delivery system (DDS) formulation was reported by Astellas Pharma [67]. The company developed a colon-targeting drug formulation [71] for YM466, a BCS class III research compound, and evaluated the in vivo performance in cynomolgus monkeys and humans. While the relative bioavailability (vs. IR formulation) of the colon-targeting dosage form was 68% in monkeys, drug absorption from the same tablets in humans was very low, with a relative bioavailability of 20%.
pH-dependent ileocolonic drug delivery, part I: in vitro and clinical evaluation of novel systems
2020, Drug Discovery TodayAdvances in orally-delivered pH-sensitive nanocarrier systems; an optimistic approach for the treatment of inflammatory bowel disease
2019, International Journal of PharmaceuticsEvaluating the clinical importance of bacterial degradation of therapeutic agents in the lower intestine of adults using adult fecal material
2018, European Journal of Pharmaceutical Sciences