(T1430-08-48) Customized Fast-Dissolving Orodispersible Films Using Extrusion-Based 3D-Printing

Purpose: The FDA defines orodispersible films (ODFs) as a thin layer dosage form that rapidly dissolves when coming into contact with water. These formulations are attractive delivery systems for the ease of fabrication, consumption handling, and transportation. ODFs are personalized dosage forms of choice for patients suffering from choking disorder or dysphagia and show rapid absorption and onset of action upon administration. An ideal ODF should be thin and flexible in applying to the tongue layer, whereas it should be sturdy enough for packaging. Industrial production of ODFs involves less efficient film casting techniques and requires post-processing and bulk manufacturing. 3D printing allows easy layer upon layer fabrication of desirable designs and allows personalization and on-demand manufacturing to create small batches at low cost on at small scale, even in compounding pharmacies. This work investigated the feasibility of two extrusion-based 3D printing technologies to fabricate the fast-dissolving orodispersible films of sumatriptan succinate. Various hydrophilic polymers were investigated as film-forming polymers to inspect the viability of both extrusion technologies in the rapid prototyping of ODF films. We investigated the effect of variation in the printing parameters, drying time, drying temperature, and nature of needle/nozzle. Our primary rationale was to compare the reproducibility and uniformity of the ODFs prepared from both printing technologies. The selection of polymers was based on a range of critical factors like rheological properties, extrudability through nozzles, consistency of flow, and drying conditions. Sumatriptan succinate (SMT), a 5-HT receptor agonist used for migraine headaches, was utilized as the model drug for investigation.

Methods: Pneumatic extrusion involves printing drug-loaded semisolid feed through needle/nozzle utilizing air pressure, whereas the syringe-pump extrusion technique utilizes mechanical extrusion to deposit a specific volume of feed material upon layer printing. Various FDA-approved polymers for oral administration like HPMC, Maltodextrin, HPC, PEO, and PVP were investigated for their printability and overall reproducibility of the process. Few hydrophilic polymers were selected to prepare the ODF batches and perform the characterization studies. The optimized parameters for printing are explained in Figure 1. The morphological characterization was done by using VHX 6000 Keyence microscope. Assay and content uniformity of SMT-ODFs was quantified using HPLC. The thickness of the films was confirmed by using calipers at three different locations of the same film. The initial screening parameters utilized are folding endurance, film brittleness, and disintegration test. The rheological behavior and viscosities of the optimized printing gels will be investigated by using Rheometer. The mechanical properties of the ODFs will be determined using a texture analyzer. The surface wettability of the finalized ODFs will be confirmed by using Static contact angle measurement.

Results: The weight uniformity of the ODFs was a crucial parameter in considering the consistency of the printing process. The SMT-ODFs obtained from both pneumatic based extrusion printing and syringe-extrusion printhead were able to consistently deliver equivalent amount compared to theoretical content. Syringe-based extrusion showed high precision for the feed deposition, thus ensuring the weight and content uniformity of the ODFs. The hydrophilic polymers selected for the initial printing trials and the preliminary observation from the batches fabrication are shown in Table 1. The batches from the hydrophilic excipients was focused on the variation in the weight and disintegration time with infill ratio (Figure 2). Pneumatic extrusion for same feed material could print an ODF film within two minutes, whereas syringe based extrusion took twice longer for printing, but was more accurate with the deposition. The presence of small air bubbles in the printing gels has a significant impact on printing by either technologies.

Conclusion: Pneumatic extrusion offered fast fabrication of ODFs, whereas syringe-pump extrusion demonstrated precision in extruded volume. Pneumatic extrusion and syringe-based extrusion have great potential in rapid personalized medicine prototyping and saving time for manufacturing. Despite some process shortcomings and various process parameters yet under investigation, both of these technologies are promising as quick fabrication tools for customized quick-dissolving ODFs for compounding settings, with a precision of feed deposition and accuracy in drug loading.


Figure 1. Printing technologies under investigation with optimized printing parameters and variable printing parameters of SMT-ODF fabrication.


Table 1. Excipient and hydrophilic polymer compatibility studies investigating the printability of the ODFs.


Figure 2. Characterization of ODF films upon fabrication- weight gain with layers, disintegration time, thickness and morphological evaluation