Continuous inkjet printing of enalapril maleate onto orodispersible film formulations

摘要

Piezoelectric inkjet printing onto orodispersible films (ODFs) was proven to be a successful technique applying flexible doses of active pharmaceutical ingredients (APIs) onto edible substrates. The reported API printing and ODF production was conducted in a non-continuous production approach. Within this study, drug-free and hydrochlorothiazide (HCT) containing ODFs should be imprinted in-line with enalapril maleate (EM) ink during continuous ODF production. Macrogol inks based on various solvents and solvent-water mixtures were developed providing dynamic viscosities from 7 to 17 mPa*s. Water based inks contained 1.25%, methanol based inks up to 10% EM. Both inks could be printed (500-1000 Hz) during continuous ODF production. No EM recrystallization was observed for water-based inks. Mechanical properties were not affected by drug printing using various firing frequencies. ODF imprinted with water-based EM inks contained 0.04 mg EM/6 cm(2). EM amount can be increased to a paediatric therapeutic dose of 0.5 mg EM utilizing methanol-based inks. These inks were successfully printed onto HCT ODFs resulting in a therapeutically relevant fixed-dose combination. No EM migration into the HCT layer could be observed. In conclusion, it was feasible to print EM doses onto drug-free and HCT ODFs during an in-line continuous manufacturing process.