Ileo-Colon Targeting of the Poorly Water-Soluble Drug Celecoxib Using a pH-Dependent Coating in Combination with Self-Emulsifying Drug Delivery or Solid Dispersion Systems.

Targeting celecoxib to the ileo-colonic region could be beneficial for the treatment and prevention of colon cancer. Ileo-colonic targeting can be achieved by using pH-dependent coating systems such as ColoPulse. Celecoxib has poor aqueous solubility, which may jeopardize optimal treatment. Therefore, we combined a pH-dependent coating with self-emulsifying drug delivery systems (SEDDS) or with solid dispersion systems (SD); two approaches that are often used to improve the dissolution behavior of lipophilic drugs. The dissolution behavior of various formulations of both systems was investigated. Optimized formulations with and without precipitation inhibitors were coated with the ColoPulse and the release of celecoxib was tested under non-sink conditions using an in vitro dissolution system, simulating the pH gradient of the gastrointestinal tract. The dissolution behavior of SDs with and without precipitation inhibitor (sodium dodecyl sulfate) and the SEDDS without precipitation inhibitor was negatively impacted by the coating. Control experiments indicated that components of the coating released in the dissolution medium acted as precipitation mediators. However, the SEDDS formulation with HPMC 4000 cps as a precipitation inhibitor showed excellent dissolution behavior. We hypothesize that HPMC accumulates at the oil/water interface of the emulsion thereby stabilizing the emulsion resulting in maintenance of the supersaturated state.

pH-dependent ileocolonic drug delivery, part II: preclinical evaluation of novel drugs and novel excipients.

Novel drugs and novel excipients in pH-dependent ileocolonic drug delivery systems have to be tested in animals. Which animal species are suitable and what in vivo methods are used to verify ileocolonic drug delivery?

pH-dependent ileocolonic drug delivery, part I: in vitro and clinical evaluation of novel systems.

After the pH dependency of novel pH-dependent ileocolonic drug delivery systems is confirmed in vitro, their performance should be evaluated in human volunteers.