The purpose of the study is to perform the in vitro and in vivo evaluation of multi-layer film coatings for omeprazole. The system consists of drug-layered or drug-containing core pellets coated with salt (sodium chloride and disodium hydrogen phosphate), hydroxypropyl methyl cellulose (HPMC), and enteric film-coating layer, respectively. The drug-layered core pellets were prepared by a coating layer of omeprazole on inert pellet cores in fluidized bed coater. An in vitro/in vivo gastro-resistance study was conducted, and a dissolution study was performed in pH 7.4 phosphate buffer for omeprazole release. The multi-layer coated pellets were stable in gastric pH conditions and upper gastrointestinal (GI) tract in rats. Salt layer improved the drug stability, and its coating levels had little influence on the dissolution profiles of omeprazole. The rate of drug release was significantly delayed by HPMC layer. The salt layer could function as a separated layer, and substitute part of the HPMC layer and decrease the coating levels of HPMC. The bioavailability (AUC) of the multi-layer coated drug-layered and drug-containing pellets was 3.48+/-0.86 and 2.97+/-0.57 microg*h/ml, respectively. The drug-layered pellets with multi-layer film coatings not only provided delayed and rapid release of omeprazole, but also could provide a good stable property for omeprazole. It was confirmed that rapid in vitro drug release rate resulted in better absorption.

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The major objectives of this study were i) to evaluate the permeability and swelling characteristics of isolated films prepared by mixing of pectin with ethylcellulose; and ii) to assess the absorption and in vitro/in vivo correlation (IVIVC) of 5-FU film-coated colon-targeted pellets in dogs. Free films were prepared by casting and solvent evaporation method. These free films were evaluated by swelling experiment and permeability to 5-FU in different media. Pectin/ethylcellulose films had suitable characteristics for colonic delivery; and when the addition of pectin was up to the ratio of 30%, the swelling and permeability of the mixed films was significantly increased in the simulated colonic fluid (SCF). Pharmacokinetic study in dogs gave T max /C max of 14 h/1.6 m mg/ml and 16 h/1.7 m mg/ml for total weight gain (TWG)-22% and 18% coated pellets, respectively. The plasma 5-FU levels of the TWG-22% and 18% coated pellets were maintained at a much lower level with a mean residence time (MRT) of 18-20 h, longer than 2.1 h for 5-FU uncoated pellets, confirming delayed absorption. There was no statistically significant difference in the area under the plasma concentration vs. times curve (AUC ) values between the uncoated pellets and the coated pellets. Moreover, a good linear regression relationship was observed between the percent in vitro dissolution in SCF and the percent absorption or percent AUC. It was concluded that i) pectin within the mixed films were susceptible to colonic enzymes, and the film-coated pellets are potentially useful for colonic drug delivery; and ii) in vitro dissolution testing in SCF could be used to establish certain IVIVC for the colon-specific drug delivery systems activated by microflora.

A general and efficient protocol for the synthesis of ortho‐halogenated tertiary benzamides under mild conditions is described. Benzamides with various functional groups underwent ortho‐iodination, bromination or chlorination with NXS using a cationic palladium catalyst generated in situ from Pd(OAc)2 and TfOH in DME. Given the generality, efficiency, mild conditions, and readily available catalyst and halogenation reagents, this method could provide a practical approach for the synthesis of ortho‐halogenated benzamides.