In-vitro and in-vivo characterisation of two sustained release formulations for the antidepressant rolipram

Using the pellet technology two sustained release formulations for (dl)-rolipram (ZK 62 711; CAS 61413-54-5) were developed and characterised by in-vitro dissolution tests and in a cross-over study in healthy male volunteers. In-vitro, 50% release was achieved within 2.5 h for formulation A and within 4 h for B. In-vivo, Cmax values of 4.4 +/- 0.9 ng/ml (A) and 2.1 +/- 0.8 ng/ml (B) were observed 2.8 +/- 0.8 h or 10.3 +/- 3.7 h after oral intake of 3 mg (dl)-rolipram. The terminal disposition half-life in the plasma was similar for both formulations (12 +/- 13 h and 11 +/- 2 h). Expectedly, the relative bioavailability of formulation B was lower compared to A (72%). Using the pellet technology, formulations with an intended release profile can be tailored to suit by mixing pellets with different release characteristics within one dosage form.