(T1430-08-49) 3D Printing of Single and Multi-unit Containers for Dispensing Solid Dosage Forms

Purpose: The two most used single and multi-unit containers for dispensing medications are blister packs and prescription bottles. Blister packets may have a paperboard or an aluminum foil backing. The plastic itself contains high-density polyethylene, polyvinyl chloride, or polypropylene. Conventional blister packs may cause issues with recycling and may not be eco-friendly. Prescription bottles are bulky with significant empty spaces in the bottle and inconvenient to carry them around. Green packaging based on biodegradable materials has currently gained great attention in the food industry. Green packaging can be made from renewable particles (e.g., cellulose fibers) or eco-friendly degradable biopolymers (e.g., polylactic acid, PLA). Yet, a barrier to designing an eco-friendly container for dispensing solid dosage forms exists because the containers manufactured with specific eco-friendly materials are less cost-effective and may have issues withstanding the mechanical and environmental stresses.
This study aimed to design, optimize, and develop a 3D-printed flexible, eco-friendly, and reusable container that stores solid dosage forms such as tablets and softgel capsules.

Methods: A single-unit container (8-unit) and a multi-unit container (4-unit) were designed using Free CAD 0.20. The rounds where tablets and capsules are stored are created by subtracting a smaller from a larger ellipsoid. Each round was separated by a long dash to help with convenient folding and cutting of the pack. The back of each container had a slit in the shape of a cross that permits easy removal of tablets and capsules. After the insertion of tablets and capsules, the back of each container was then sealed with adhesive water-resistant papers. Flashforge Adventurer Pro 3 was used to 3D-print 8-unit and 4-unit containers. The extruder temperature was set at 210°C, and platform was maintained at 50°C. Infill density was 15%, layer height was 0.18 mm, and base print speed was kept at 60 mm/s. Flexible PLA 1.75mm filament was used as a printing material.3D-printed containers were classified based on evaluating the moisture-permeation characteristics of the containers observed at 75 ± 3% relative humidity and at a temperature of 23 ± 2°C. The containers were designated Class A if no containers tested exceeds 0.5 mg per day in average moisture permeation rate; they are designated Class B if no containers tested exceeds 5 mg per day in average moisture permeation rate; they are designated Class C if no containers tested exceeds 20 mg per day in average moisture permeation rate; and they are designated Class D if the containers tested meet none of the above average moisture permeation rate requirements. To test whether 3D printed containers provide adequate protection from the environment as the dosage form is distributed and stored, a few model dosage forms, ibuprofen 200 mg tablets, dextromethorphan HBr 15 mg softgel capsules, and guaifenesin 600 mg tablets, were used. For 3D-printed 8-unit, single-unit containers, individual ibuprofen tablets were inserted into each round. For 3D-printed 4-unit, multi-unit containers, an ibuprofen tablet, a dextromethorphan HBr softgel capsule, and a guaifenesin tablet were inserted into each round. For the controls, all three dosage forms were stored in 8-dram polypropylene prescription bottles. The containers carrying dosage forms were stored in accelerated condition at 75 ± 5% relative humidity and at a temperature of 40 ± 2°C. Model drugs stored in 3D-printed single- and multi-unit containers as well as prescription bottles were collected for 0, 1, and 2 months and treated to prepare the samples appropriate for HPLC analyses.

Results: Single-unit (8-unit) and multi-unit (4-unit) containers were designed using CAD program and successfully 3D-printed (Figure 1). The printed containers were flexible and easy to bend and fold (Figure 2). Tablets and softgel capsules were inserted into and removed from 3D-printed containers through the bottom slit. Both containers were sealed with adhesive, water-resistant papers. The printing times were 1 h and 39 min for an 8-unit container and 2 h and 7 min for a 4-unit container. Moisture permeation study results demonstrated that both 3D-printed containers are categorized into Class D as containers tested demonstrated average moisture permeation rates greater than 20 mg/day (8 unit: 24.475 ± 8.62 mg/day, 4 unit: 32.75 ± 7.02 mg/day). Less than 3% of the API was lost in 2 months from the solid dosage forms when stored in new and used (used for a month to store tablets) 4-unit and 8-unit containers.

Conclusion: Single-unit (8-unit) and multi-unit (4-unit) containers were successfully built by using (fused deposition modeling (FDM), also known as fused filament fabrication (FFF) 3D printing. Although the significant loss of the API from the tablets and softgel capsules was not observed when stored in 3D-printed containers, the printing speed and the absorption of water must be revisited to improve the 3D printing process and the quality of the container.

Figure 1. CAD design of 8-unit and 4-unit containers, isometric (A), top (B) and bottom (C) views.

Figure 2. 3D-printed 4-unit and 8-unit containers, top (A), bottom (B), and folded (C) views.