Direct compression and moulding properties of co-extruded isomalt/drug mixtures.

Isomalt, a disaccharide alcohol was co-extruded with paracetamol or hydrochlorothiazide (HCT) in order to improve its tabletting properties. After extrusion, isomalt was transformed into an amorphous form, while paracetamol remained crystalline. Hot stage microscopy showed that HCT was amorphous in the isomalt carrier up to a concentration of 1% (w/w). Direct compression of mixtures formulated with co-extruded isomalt/paracetamol powders yielded harder tablets compared with physical mixtures and no powder agglomeration was observed. Direct moulding of isomalt co-extruded with either paracetamol or HCT was feasible, yielding hard tablets. A fast dissolution rate was seen for both the compressed and the moulded tablets (>80% paracetamol and 60% HCT released within 20 min). The compressed tablets showed a dramatic decrease in tensile strength during storage at 85% RH, while the tensile strength of the moulded tablets remained above 0.80 MPa after 6 months storage at the same conditions. Co-extrusion of isomalt with paracetamol and HCT dramatically improved the tabletting properties of the mixtures (compared with physical mixtures of drug and isomalt). Direct moulding proved to be a suitable technique to produce isomalt based tablets.