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.

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Materials: Celecoxib (CXB), Eudragit S100, and hydroxypropyl methylcellulose acetate succinate LG (HPMCAS-LG) were supplied by Jansen Pharmaceutica (Beerse, Belgium). Capryol 90, Maisine CC, Peceol, Plurol oleique CC 497, and Labrasol were a gift from Gattefossé (Saint-Priest Cedex, France). Captex 200 P, Captex 355 EP/NF, and Capmul PG-8 NF were a gift from ABITEC Corporation (Columbus, OH, USA). Croscarmellose sodium (AcDiSol) was obtained from FMC BioPolymer (Philadelphia, PA, USA). Tween 20, isopropyl myristate, Cremophor RH40, PEG 400, tetraglycol, Patent Blue V, Povidone (PVP) K15, PVP K60, and PVP K90 were obtained from Sigma-Aldrich (St. Louis, MO, USA). Gelatine Licaps^® size 0 capsules were gifted by Capsugel (Bornem, Belgium). Macrogolum 6000 (PEG 6000), PVP K30, hydroxypropyl methylcellulose (HPMC) 5 and 4000 cps, talc, and gelatine were obtained from BUFA (IJsselstein, The Netherlands). Tween 80, 37% fuming hydrochloric acid, sodium chloride (NaCl), sodium dodecyl sulfate (SDS), tert-butyl alcohol (TBA), sodium dihydrogen phosphate dihydrate, and sodium hydroxide (NaOH) were obtained from MERCK (Darmstadt, Germany). Acetone and ethanol 70% were purchased from BOOM B.V. (Meppel, The Netherlands) and methanol from VWR Chemicals (Fontenay-sous-Bois, France). Millipore type 1 water was used in all experiments except for the dissolution media where demineralized water was used.

Article information: Broesder, A.; Berends, J.M.E.; Scheepers, S.M.; Nguyen, D.N.; Frijlink, H.W.; Hinrichs, W.L.J. 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. Pharmaceutics 2021, 13, 731. https://doi.org/10.3390/pharmaceutics13050731