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The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

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.