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

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.

Comparative investigations on key factors and print head designs for pharmaceutical inkjet printing.

The interest in using inkjet printing as manufacturing technology for personalized medicine has increased in recent years. The print head is the centrepiece of an inkjet printer. For pharmaceutical approaches, various types of printing equipment were tested in the past, but comparative investigations in relation to pharmaceutical use are still lacking. In the present study, two piezoelectric print heads of different designs (Spectra SE-128 AA and Konica Minolta KM512SHX) were systematically compared with the objective of deepening the process understanding and identifying the key factors on the resulted quantities. As substrates, oral thin films made from 15% (w/w) hypromellose (HPMC) casting solution were used. The Spectra print head with bigger nozzles was more efficient in one pass and resulted in less scattering (RSD ≤ 5%). Furthermore, it was found that liquid excipients like polyethylene glycol 400 characterized by low vapour pressure and limited penetration into the HPMC based films are not suitable. The choice of the printed geometry plays a subordinate role when printing the same surface area, whereas the composition of the inks, set process parameters as well as the size and functionality of the nozzles have a significant impact on the final printed quantity.

A Pediatrics Utilization Study in The Netherlands to Identify Active Pharmaceutical Ingredients Suitable for Inkjet Printing on Orodispersible Films.

BACKGROUND: The use of medication in pediatrics, children aged 0-5 years, was explored so as to identify active pharmaceutical ingredients (APIs) suitable for inkjet printing on a plain orodispersible film (ODF) formulation in a pharmacy. METHODS: The database IADB.nl, containing pharmacy dispensing data from community pharmacies in the Netherlands, was used to explore medication use in the age group of 0-5 years old, based on the Anatomical Therapeutic Chemical classification code (ATC code). Subsequently, a stepwise approach with four exclusion steps was used to identify the drug candidates for ODF formulation development. RESULTS: there were 612 Active Pharmaceutical Ingredients (APIs) that were dispensed to the target group, mostly antibiotics. Of the APIs, 221 were not registered for pediatrics, but were used off-label. After the exclusion steps, 34 APIs were examined regarding their suitability for inkjet printing. Almost all of the APIs were sparingly water soluble to practically insoluble. CONCLUSION: Pharmaceutical inkjet printing is a suitable new technique for ODF manufacturing for pediatric application, however the maximal printed dose as found in the literature remained low. From the selected candidates, only montelukast shows a sufficiently high water-solubility to prepare a water-based solution. To achieve higher drug loads per ODF is ambitious, but is theoretically possible by printing multiple layers, using highly water-soluble APIs or highly loaded suspensions.

Oromucosal films: from patient centricity to production by printing techniques.

Introduction: Oromucosal films, comprising mucoadhesive buccal films (MBFs) and orodispersible films (ODFs), are considered patient-centric dosage forms. Target groups are patients with special needs. Various active pharmaceutical ingredients have been shown to be suitable for oromucosal film production. A shift is seen in the production techniques, from conventional solvent casting to printing techniques. Areas covered: In this review, the patient acceptability of oromucosal films is discussed. An overview is given of the small molecule drugs, biopharmaceuticals and herbal extracts that have been incorporated so far. Finally, the current state of 2D and 3D printing techniques for production purposes is discussed. Expert opinion: The patient-centric features are important for the further development and acceptance of this oral solid dosage form. Oromucosal films perfectly fit in the current attention for personalized medicine. Both MBFs and ODFs are intended for either a local or a systemic effect. For buccal absorption, sufficient mucoadhesion is one of the most important criteria an oromucosal film must comply with. For the preparation, the solvent casting technique is still predominately used. Some limitations of this production method can be tackled by printing techniques. However, these novel techniques introduce new requirements, yet to be set, for oromucosal film preparation.