Abstract. The different approaches for targeting orally administered drugs to the colon include coating with pH-dependent polymers, design of time-release dosage forms, and the utilization of carriers that are degraded exclusively by colonic bacteria. The aim of the present study was to develop a single unit, sitespecific drug formulation allowing targeted drug release in the colon. Matrix tablets were prepared by wet granulation using cross-linked chitosan (ChI) and chondroitin sulfate (ChS) polysaccharides as binder and carrier. ChS was used to form polyelectrolyte complexes (PEC) with ChI, and its potential as a colon-targeted drug carrier was investigated. Indomethacin was used as a model drug. The ChI and ChS PEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction studies (XRD). The matrix tablets were tested in vitro for their suitability as colon-specific drug delivery systems. FTIR demonstrated that the PEC forms through an electrostatic interaction between the protonated amine (NH 3 + ) group of ChI with the free carboxylate (COO − ) group and sulfate (SO 4 2− ) group of ChS. DSC and XRD indicated that the PEC has different thermal characteristics from ChI or ChS. The dissolution data demonstrates that the dissolution rate of the tablet is dependent upon the concentration of polysaccharide used as binder and matrix and time of cross-linking. The study confirmed that selective delivery of indomethacin to the colon can be achieved using cross-linked ChI and ChS polysaccharides.

The objective of this study was to investigate a novel hydrogel plug using isolated root mucilage of Sterculia urens to obtain a desired lag time for an oral chronotherapeutic colon-specific pulsatile drug delivery of indomethacin. Pulsatile drug delivery was developed using chemically treated hard gelatin capsule bodies filled with eudragit multiparticulates of indomethacin, and sealed with different hydrogel plugs (root mucilage of S. urens, xanthan gum, guar gum, HPMC K4M and combination of maltodextrin with guar gum). Indomethacin multiparticulates were prepared using extrusion spheronization, spray drying and solvent evaporation techniques with Eudragit® L-100 and S-100 (1:2) by varying drug-to-polymer ratio. After oral administration, the water-soluble cap of capsule dissolved in the intestinal fluid and the hydrogel plug swells. After a controlled time, the swollen plug subsequently ejected from the dosage form, releases the contents of the capsule. The formulation factors affecting the drug release were concentration and types of hydrogel plug used. In vivo gamma scintigraphy study in healthy rabbits proved the capability of the system to release drug in lower parts of the gastrointestinal tract after a programmed lag time. This study demonstrates that the indomethacin multiparticulates could be successfully colon-targeted by the design of time and pH-dependent modified chronopharmaceutical formulation. In conclusion, the investigated novel hydrogel plug could be a valuable tool for achieving desired lag time.

Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.