Development of an extended-release formulation of capecitabine making use of in vitro-in vivo correlation modelling

Jelte Meulenaar, Ron J. Keizer, Jos H. Beijnen, Jan H.M. Schellens, Alwin D.R. Huitema, Bastiaan Nuijen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

7 Citaten (Scopus)


An oral extended-release (ER) formulation of capecitabine was developed for twice daily dosing, theoretically providing a continuous exposure to capecitabine, thus avoiding the undesirable in-between dosing gap inherent to the dosing schedule of the marketed capecitabine immediate-release formulation (Xeloda® ). The target 12-hour in vivo release profile was correlated to an in vitro dissolution profile using an in vitro-in vivo correlation model based on the pharmacokinetic (PK) and dissolution characteristics of Xeloda®. Making use of the slow dissolution characteristics of amorphous capecitabine as reported previously and screening of a panel of ER excipients, an ER formulation was designed. Kollidon®SR induced the most prominent ER. Moreover, it was shown that tablets prepared from CoSD capecitabine and Kollidon®SR have an additional threefold delay in dissolution compared with tablets prepared from the same but only physically mixed components. Therefore, a prototype tablet formulation composed of co-spray-dried capecitabine and Kollidon®SR (98/2%, w/w) mixed with colloidal silicon dioxide (0.5%, w/w) and magnesium stearate (2.5%, w/w) was defined. This prototype shows similar dissolution characteristics as the modelled dissolution profile. Currently, the in vivo PK of our designed ER capecitabine formulations is investigated in a clinical study.

Originele taal-2Engels
Pagina's (van-tot)478-484
Aantal pagina's7
TijdschriftJournal of Pharmaceutical Sciences
Nummer van het tijdschrift2
StatusGepubliceerd - feb. 2014
Extern gepubliceerdJa


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