Hot-melt Ram extrusion 3D printing: a smart method for compounding orodispersible films in hospital pharmacies

Background: Orodispersible films (ODF) have been proposed as a valid alternative to conventional oral dosage forms to personalize the therapies and to improve the patient adherence, especially in special populations (e.g., dysphagics, paediatrics, geriatrics). Since manufacturing technologies used by the industries (e.g., solvent casting technique) cannot be easily applied in a pharmacy setting, alternative methods have been proposed for compounding. 3D-printing permits to prepare ODF of different strengths and geometries that fulfil the Ph.Eur. specifications about uniformity of dosage units. Purpose: To demonstrate the feasibility of the preparation of ODF by hot-melt ram extrusion 3D printing [1]. Material and method: This novel technology consists of three simple operations. First, maltodextrins, drug, and other excipients (e.g., colourants, flavours, sweeteners) are mixed in a mortar and wetted with the plasticizer (i.e., glycerine). Then, the mixture is fed into the chamber of the ram-extruder and heated. ODF are individually printed using an 18G needle on the packaging material foil and sealed without further manipulations. The critical formulation attributes and process variables were investigated to define the processability space and their impact on the disintegration time and tensile properties of the ODF. The paracetamol (PAR) was used as model drug to assess the drug loading capacity of the ODF and the dissolution profile. Results: Preliminary results allowed to optimize the process parameters (heating temperature, 85°C; maximum print rate, 50 mm/s; filling angle, 120°) and composition (maltodextrins/glycerine: 80/20 w/w) to obtain homogeneous ODF. The compounded ODF (6 cm2; thickness 150-250 μm) disintegrated in less than 1 min and showed acceptable tensile properties for product handling. Different doses of PAR (12.5, 25, 37.5% w/w) were loaded to such basic composition without altering the ODF performances. The CV% of PAR assay remains lower than 5%. The PAR dissolution profile of printed ODF (t80 < 6min) overlapped that obtained by ODF prepared by solvent casting technique [1]. Conclusions: The overall results suggested that hot-melt ram extrusion 3D printing can be used in a pharmacy setting to prepare well-accepted orodispersible dosage forms and to personalize the drug dose according to the patient needs. References: [1] Musazzi et al., Int J Pharm, 2018, 551, 52-59