Fundamental Investigations into Metoprolol Tartrate Deposition on Orodispersible Films by Inkjet Printing for Individualised Drug Dosing

Abstract

Individualised medicine is continuously gaining attention in pharmaceutical research. New concepts and manufacturing technologies are required to realise this therapeutic approach. Off-label drugs used in paediatrics, such as metoprolol tartrate (MPT), are potential candidates for innovations in this context. Orodispersible films (ODFs) have been shown as an accepted alternative dosage form during the last years and inkjet printing is traded as seminal technology of precise deposition of active pharmaceutical ingredients (APIs). The objective of this study was to combine both technologies by developing imprinted ODFs based on hypromellose with therapeutically reasonable MPT single doses of 0.35 to 3.5 mg for paediatric use. After preselection, suitable ink compositions were analysed by confocal Raman microscopy regarding MPT distribution within the imprinted ODFs. Adjusted print settings, speed, print direction and angle, characterised the final ODF surface structure. The present investigations show that uniform dosages with acceptance values between 1 and 6 can be achieved. Nevertheless, changes in calibrated printed quantity due to nozzle aging have a significant effect on the final applied dose. At the lowest investigated quantity, the RSD was ±28% and at the highest, ±9%. This has to be considered for implementation of inkjet printing as a pharmaceutical production tool in the future.

3D Printing of Pediatric Medication: The End of Bad Tasting Oral Liquids?—A Scoping Review

“…Dose accuracy was defined with content uniformity [30][31][32][33]39,52,54] or drug content assay [34][35][36][40][41][42][43][44][45][55][56][57][58]. Alternatively, one study determined the uniformity of dosage units using the mass variation method of the European Pharmacopoeia (Ph.…”

“…For inkjet printing and drop-on-solid 3D printing, the concentration of the drug in the printing ink can be altered to adjust to printed dose [52,55,56]. Furthermore, for inkjet printing, the printing size [33,55,59], the printing resolution [54] and the number of printed ink layers [55,58,59] determined the drug loading on the edible film. One study also determined the feasibility of using the number of printed ink layers for drop-on-powder 3D printing [52].…”

“…Orodispersible films were typically produced using inkjet printers [33,[54][55][56][57][58][59], or with extrusion 3D printers [32,33,36,45]. The drug containing ink is printed onto a carrier film layer.…”

“…Various studies substantiated the medical need for choosing a specific API. Most often the current need for manipulation or preparation of oral drugs was mentioned [30,32,33,40,[48][49][50]52,54]. In extension, the current lack of personalized oral dosages were also often mentioned [31,36,[55][56][57]59].…”

“…The identified model drugs were often indicated for the treatment of cardiovascular events and diseases [30,33,35,36,39,46,48,52,54,57,59]. Drugs used for the treatment of epilepsy and related diseases [31,37,43,53,56], and pain reduction and peri-operative treatment drugs [34,41,45,51] were also often used as model drugs in the studies.…”