2017 Volume 40 Issue 3 Pages 357-364
Three-dimensional (3D) printers have been applied in many fields, including engineering and the medical sciences. In the pharmaceutical field, approval of the first 3D-printed tablet by the U.S. Food and Drug Administration in 2015 has attracted interest in the manufacture of tablets and drugs by 3D printing techniques as a means of delivering tailor-made drugs in the future. In current study, polyvinylalcohol (PVA)-based tablets were prepared using a fused-deposition-modeling-type 3D printer and the effect of 3D printing conditions on tablet production was investigated. Curcumin, a model drug/fluorescent marker, was loaded into PVA-filament. We found that several printing parameters, such as the rate of extruding PVA (flow rate), can affect the formability of the resulting PVA-tablets. The 3D-printing temperature is controlled by heating the print nozzle and was shown to affect the color of the tablets and their curcumin content. PVA-based infilled tablets with different densities were prepared by changing the fill density as a printing parameter. Tablets with lower fill density floated in an aqueous solution and their curcumin content tended to dissolve faster. These findings will be useful in developing drug-loaded PVA-based 3D objects and other polymer-based articles prepared using fused-deposition-modeling-type 3D printers.
The production of various objects by three-dimensional (3D) printers has developed extensively as the printers have evolved.1,2) 3D printers are used by the creator to rapidly design prototype parts and can thus considerably cut production times and costs. 3D printers have been used to manufacture parts for cars, home electronic devices, aircraft engines, buildings, and for other practical uses. It is speculated that 3D printers have potential for many applications and that the 3D printer market will expand.
The medical applications of 3D printers have been expanding and bringing innovation to the field.3) For example, the 3D printing of organs and body parts is used to provide blueprints4) for surgeons and patients to understand disease sites.5–7) In addition, bioprinting, which involves the placement of cells, proteins and genes on a substrate, is also being conducted in the anticipation of future applications in tissue engineering.8,9) Future artificial organs and implantable devices are also being designed.10,11) In the pharmaceutical industry, a new tablet (SPRITAM®, a rapid disintegrating tablet containing levetiracetam) prepared by 3D printing was approved by the U.S. Food and Drug Administration (FDA) in 2015.12) The application of 3D printing in medicine, including tablets, holds promise for made-to-order drugs and removes mass product manufacturing from the production line, although the technology in pharmaceutical industry is still in infancy.13) Moreover, it is predicted that the internet of things (IoT) will increase the future use of 3D printers by reinforcing manufacturing control.
Model objects are typically prepared by laminating materials from the nozzle of a 3D printer. There are different types of 3D printers,2) such as fused deposition modeling (FDM), stereo lithography, selective laser sintering, binder jetting, inkjet, and projection printers. An FDM 3D printer manufactures an object by laminating a thermoplastic resin (such as polylactic acid and acrylonitrile butadiene styrene) using heat. FDM 3D printers are now off-patent, inexpensive, and widely available.
In the present study, we investigated the effect of 3D printing parameters on the formability of polyvinylalcohol (PVA)-based tablets. PVA is commonly used as a support for the 3D printing of objects and because it is water soluble, it can be easily removed from an object by washing with water. PVA is also a common excipient in tablets and is used as a binder in the pharmaceutical industry.14) There are several early reports of PVA-based tablets,15–19) but it remains unclear how the printing conditions used with an FDM 3D-type printer affects the formability of the printed tablets. We designed tablets under different conditions using 3D computer-aided-design (CAD) software and set different 3D printing conditions by using slicer software. We used curcumin, a familiar compound extracted from turmeric and exhibiting many pharmacological effects, as a model drug.20,21) Curcumin is fluorescent and thus should act as a fluorescent marker. PVA and curcumin-loaded PVA tablets were investigated in this study.
Synthetic curcumin was purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Commercially available PVA filament was purchased from Nippon Synthetic Chemical Industry Co., Ltd. (Osaka, Japan).
Preparation of Curcumin-Loaded PVA FilamentCurcumin-loaded filament was prepared using a soaking method as previously described.17) Briefly, an approximately 5 m rolled PVA filament was soaked in 5 mg/mL curcumin-saturated ethanol solution in a container and incubated at room temperature overnight. The sample was then dried in an oven at 60°C for more than 1.5 h. The PVA and curcumin-loaded PVA filaments were kept in a desiccator until use. The mean amount of curcumin loaded into the PVA filament was 1750±230 µg/g filament. The appearance of the PVA and curcumin-loaded PVA filaments is shown in Fig. 1A.
Tablets were designed using 3D CAD software (123D Design; Autodesk Inc., San Rafael, CA, U.S.A.). A cylinder 10 mm in diameter and 3 mm thick was designed as a typical tablet (Fig. 1B). The design data were saved as a standard template library (STL) file. The STL file was converted into the printer control code ‘g-code’ using Cura 3D printing slicing software (Ultimaker; Geldermalsen, the Netherlands). Typical printing conditions set by the software were: printing speed, 20 mm/s; top/bottom thickness, 0.8 mm; shell thickness, and 0.4 mm. During printing, the percent flow we described “flow rate” was increased from 90 to 140%, the printing temperature was increased from 140 to 250°C, the bed temperature was fixed at 60°C, and the fill density was increased from 0 to 100%. The printing time was approximately 2 min for a tablet 10 mm in diameter, 3 mm thick, and with a fill density of 100%. Samples were 3D-printed using an FDM-type 3D printer (FDM-200W, NinjaBot, Shizuoka, Japan) controlled by Pronterface 3D printing host software (GNU General Public License).
Characterization of PVA and Curcumin-Loaded PVA TabletsThe resulting tablets produced as described in “3D Printer, Software and Printing Conditions” were weighed on an electronic balance. The mean diameters and thicknesses of the tablets were calculated by randomly measuring three points using a digital caliper. The mean volume of the tablets was calculated from the mean diameter and thickness and the mean density was calculated from the mean weight and volume by simple math. Curcumin-loaded PVA filament was dissolved in 0.1% Tween 80 aqueous solution, then the amount of incorporated curcumin was determined from the fluorescence of the dissolved curcumin (ex 485 nm/em 535 nm) using a plate reader (Wallac 1420 ARVO, PerkinElmer, Inc., Waltham, MA, U.S.A.). PVA filament was similarly dissolved and its fluorescence intensity was subtracted as background.
Powder X-Ray Diffraction (PXRD)The PVA and curcumin-loaded PVA filaments were pulverized and the crystallinities of the PVA, curcumin-loaded PVA and curcumin powders were analyzed using an X-ray diffractometer (Rint-Ultima, Rigaku Co., Ltd., Tokyo, Japan) in the 2θ range from 5 to 35° using CuKα radiation.
Differential Scanning Calorimetry (DSC)Thermal analysis was conducted using a Shimadzu DSC-50 (Shimadzu, Kyoto, Japan). The PVA and curcumin-loaded PVA filaments were pulverized. Approximately 2–3 mg samples were placed in aluminum pans with seals and crimped. The samples were heated at a heating rate of 10°C/min ranging from 50 to 250°C.
Dissolution TestDissolution tests were conducted using a NT-40H disintegration tester (Toyama Sangyo, Osaka, Japan) and the paddle method described in Japanese Pharmacopoeia 17th edition. In brief, each vessel of the disintegration tester was filled with 500 mL water for testing PVA tablets, or 500 mL of 0.1% Tween 80 aqueous solution for testing curcumin-loaded PVA tablets. The temperature was maintained at 37°C and the solvents were mixed at 100 rpm. Then, a PVA (or curcumin-loaded PVA) tablet was placed in each vessel. At appropriate time points (0, 15, 30, 45, 60, 90, 120, 180, 240 min), samples were withdrawn. The sample solutions treated with PVA tablets were used for determination without filtration, while the sample solutions treated with curcumin-loaded PVA tablets were passed through 0.45 µm membrane filter. The dissolution of PVA tablets was determined by measuring the absorbance of the resulting PVA solution at 505 nm as turbidity. The concentration of curcumin released from curcumin-PVA tablets was determined by measuring the fluorescence of the curcumin, as described in “Characterization of PVA and Curcumin-Loaded PVA Tablets.” The floating properties of the tablets were visually assessed by placing tablets individually in separate dissolution test apparatus vessels and monitoring the floating conditions of tablets with different fill densities over time.
In this study, curcumin was used as a model drug and tablets containing curcumin were prepared. Curcumin is a major component of turmeric extract and exhibits many pharmacological effects, including anti-oxidative and anti-inflammation effects.20,21) Curcumin was loaded into PVA filaments using a soaking method described previously.17) Two methods have been reported for the preparation of drug-loaded PVA filaments using FDM-type 3D printers: the hot-melt extrusion method18,22) and the soaking method.15,17) Hot-melt extrusion is an established method that uses an extruder.23,24) In contrast, the soaking method involves the simple soaking of a polymer filament in organic solvent saturated with the drug (in this case, a drug ethanoic solution) and the drug diffuses into the polymer filament. The soaking method is limited to drugs soluble in organic solvent, and the resulting loaded amount of drug is lower than obtained using the hot-melt extrusion method. However, this simple method is advantageous in that it does not require a heating process nor an expensive extruder instrument. PVA filament (white) and curcumin-loaded PVA filament (yellow) are shown (Fig. 1A). A small amount of curcumin (1750±230 µg) was loaded per gram of polymer in current experimental condition. We anticipate that this method may be applicable for drugs exhibiting a therapeutic effect at low dose. Curcumin was used in the current study due to its yellow color and fluorescent properties in order to understand the dissolution characteristics of the PVA tablets.
The suitability of the 3D printing system for accurately generating the desired sizes of tablets was tested by designing and printing tablets ranging from 5 to 15 mm in diameter (Fig. 2, Table 1). PVA and curcumin-loaded PVA tablets were accurately produced reproducibly, with the mean diameter and thickness differing by ±5% of the target values. The densities of the tablets ranged from 1.00–1.10 mg/mm3 (g/cm3). The density of commercially available PVA filament used in the present study was lower than that of typical PVA (1.3 g/cm3, from the Merck Millipore homepage), suggesting that plasticizing polymers had been added. Use of current 3D printer systems for small objects is rather challenging and thus slighter larger than expected curcumin-loaded PVA tablets were obtained when the target diameter was set to 5 mm (5.30±0.17 mm, corresponding to 106.0±3.3% in Table 1). These results suggest that this should be taken into account when designing the print parameters for small objects. Regardless, the present results demonstrate the promise of printing small tablets.25)
(A) PVA tablets. (B) Curcumin-loaded PVA tablets. The thicknesses of all tablets were set to 3 mm. The printing conditions for the 3D printing slicer software were as follows: printing temperature, 210°C; flow rate, 120%; fill density, 100%.
| (A) PVA tablets | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | |
| Diameter (%) | 103.6±1.2 | 103.0±1.0 | 102.0±1.9 | 102.5±0.5 | 102.0±0.6 | 102.1±0.3 | 102.1±0.5 | 101.9±1.2 | 101.5±0.9 | 101.0±0.5 | 101.0±0.3 |
| Thickness (%) | 96.9±1.7 | 98.1±2.3 | 98.6±4.1 | 97.8±2.2 | 97.3±3.6 | 97.6±2.3 | 97.9±3.3 | 98.1±3.0 | 98.4±1.8 | 98.5±2.0 | 97.9±1.2 |
| Weight (mg) | 65.7±1.6 | 95.6±0.9 | 129.5±1.0 | 168.7±1.6 | 211.5±3.8 | 260.6±2.4 | 313.4±4.1 | 375.0±3.8 | 442.4±1.5 | 507.9±3.4 | 582.5±2.9 |
| Density (mg/mm3) | 1.07±0.03 | 1.08±0.01 | 1.09±0.01 | 1.09±0.01 | 1.10±0.02 | 1.09±0.01 | 1.08±0.02 | 1.09±0.02 | 1.10±0.01 | 1.09±0.01 | 1.10±0.01 |
| (B) Curcumin-loaded tablets | |||||||||||
| 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | |
| Diameter (%) | 106.0±3.3 | 103.3±1.8 | 103.1±1.9 | 102.4±2.1 | 101.9±0.9 | 101.8±1.1 | 101.6±0.7 | 101.0±0.9 | 101.4±0.7 | 101.8±0.8 | 101.5±0.5 |
| Thickness (%) | 96.3±2.7 | 98.2±4.1 | 98.6±4.4 | 98.1±5.6 | 99.1±3.4 | 99.2±3.3 | 99.2±3.8 | 98.4±4.2 | 97.5±4.1 | 97.7±2.3 | 96.6±3.1 |
| Weight (mg) | 65.5±3.4 | 94.2±2.7 | 126.7±7.1 | 164.8±12.1 | 209.7±5.2 | 258.0±6.2 | 310.3±8.5 | 367.7±8.3 | 427.7±12.9 | 495.6±21.7 | 566.9±21.9 |
| Density (mg/mm3) | 1.03±0.03 | 1.06±0.03 | 1.05±0.04 | 1.06±0.02 | 1.07±0.02 | 1.07±0.02 | 1.06±0.03 | 1.08±0.03 | 1.07±0.02 | 1.06±0.04 | 1.07±0.02 |
The thicknesses of all tablets were set to 3 mm. Data represent the mean±standard deviation (S.D.) (n=5).
After designing a 3D object using, for example, 3D CAD software, the printing conditions are set and programmed using 3D printer slicer software such as g-code. Previous reports provided little information regarding the 3D-printing parameters and thus we investigated the effects of several printing conditions. We found that flow rate, the parameter that controls the extruded amount of polymer filament, affected the formability of PVA and curcumin-loaded PVA tablets (Fig. 3, Table 2). Low flow rates (90, 100%), provided tablets with lower density (PVA tablet; 90%, 0.90±0.02 mg/mm3; 100%, 0.97±0.02 mg/mm3: curcumin-loaded PVA tablet; 90%, 0.88±0.04 mg/mm3; 100%, 0.96±0.04 mg/mm3, Table 2), perhaps due to the production of thinner tablets. In contrast, a high flow rate (140%) provided tablets with rough surfaces and wider thicknesses (PVA tablet, 112.9±2.4%; curcumin-loaded PVA tablet; 114.7±4.0%, Table 2). Tablets with rough surfaces create space irregularly, resulting in lower density (curcumin-loaded PVA tablet; 140%, 0.99±0.04 mg/mm3, Table 2). We set the flow rate to 120% for subsequent experiments.
(A) PVA tablets. (B) Curcumin-loaded PVA tablets. The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions for the 3D printing slicer software were as follows: printing temperature, 210°C; fill density, 100%.
| (A) PVA tablets | ||||||
|---|---|---|---|---|---|---|
| % | 90 | 100 | 110 | 120 | 130 | 140 |
| Diameter (%) | 99.2±0.5 | 99.5±0.8 | 100.2±0.9 | 101.4±0.9 | 103.0±0.8 | 104.8±0.9 |
| Thickness (%) | 95.3±1.3 | 96.6±1.2 | 95.7±1.5 | 99.2±1.5 | 106.0±1.7 | 112.9±2.4 |
| Weight (mg) | 198.3±2.4 | 219.3±1.5 | 241.8±1.7 | 263.5±1.0 | 283.3±1.5 | 303.8±1.8 |
| Density (mg/mm3) | 0.90±0.02 | 0.97±0.02 | 1.07±0.01 | 1.10±0.02 | 1.07±0.01 | 1.04±0.02 |
| (B) Curcumin-loaded tablets | ||||||
| % | 90 | 100 | 110 | 120 | 130 | 140 |
| Diameter (%) | 99.1±0.7 | 99.9±0.5 | 100.5±0.9 | 101.9±1.2 | 103.3±0.5 | 106.3±1.5 |
| Thickness (%) | 94.2±1.7 | 95.3±0.8 | 95.6±1.1 | 100.3±3.1 | 108.9± 2.0 | 114.7±4.0 |
| Weight (mg) | 191.4±4.8 | 214.8±7.5 | 235.2±7.5 | 256.9±7.7 | 276.4±7.6 | 302.2±6.1 |
| Density (mg/mm3) | 0.88±0.04 | 0.96±0.04 | 1.03±0.04 | 1.05±0.04 | 1.01±0.04 | 0.99±0.04 |
The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions were set by the 3D printing slicer software. Data represent the mean±S.D. (n=5).
The printing temperature, which is the temperature of the nozzle that extrudes the PVA filament or curcumin-loaded PVA filament, was changed from 140 to 250°C and PVA tablets and curcumin-loaded PVA tablets were prepared (Fig. 4, Table 3). No tablets were prepared at nozzle temperatures <140°C since the filament extrudes poorly below this temperature. We had expected that the extruded amounts of PVA and curcumin-loaded PVA filament would increase with increasing temperature due to an increase in fluidity, but this was not observed, suggesting that the production of 3D objects using the current system is controlled well by flow rate, as mentioned above. However, the color of the produced curcumin-loaded PVA tablets decreased remarkably with increasing temperature (Fig. 4), suggesting thermal and oxidative degradation of the curcumin, as previously reported.26,27) To solve the problems, the careful selection of optimal printing temperature is important and would prevent the drug degradation in PVA filament which was prepared by soaking methods.
(A) PVA tablets. (B) Curcumin-loaded PVA tablets. The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions for the 3D printing slicer software were as follows: flow rate, 120%; fill density, 100%.
| (A) PVA tablets | ||||||
|---|---|---|---|---|---|---|
| °C | 140 | 150 | 160 | 170 | 180 | 190 |
| Diameter (%) | n/a | 98.8±0.5 | 100.4±0.4 | 100.2±0.7 | 100.7±0.6 | 101.8±1.5 |
| Thickness (%) | n/a | 94.7±2.6 | 94.2±2.1 | 94.7±0.9 | 96.6±2.2 | 94.6±1.3 |
| Weight (mg) | n/a | 236.9±5.1 | 244.6±2.1 | 246.5±2.4 | 250.0±4.1 | 250.4±2.1 |
| Density (mg/mm3) | n/a | 1.09±0.02 | 1.09±0.02 | 1.10±0.01 | 1.08±0.02 | 1.09±0.03 |
| °C | 200 | 210 | 220 | 230 | 240 | 250 |
| Diameter (%) | 101.4±1.6 | 102.5±1.4 | 102.8±1.4 | 103.0±1.4 | 103.5±0.9 | 104.6±1.3 |
| Thickness (%) | 96.8±0.7 | 96.3±1.2 | 96.4±2.0 | 97.6±0.7 | 95.3±1.8 | 96.1±3.4 |
| Weight (mg) | 248.9±2.1 | 250.4±4.6 | 248.5±1.2 | 251.7±3.6 | 249.4±4.3 | 253.6±7.6 |
| Density (mg/mm3) | 1.06±0.03 | 1.05±0.05 | 1.04±0.04 | 1.03±0.03 | 1.04±0.04 | 1.02±0.02 |
| (B) Curcumin-loaded tablets | ||||||
| °C | 140 | 150 | 160 | 170 | 180 | 190 |
| Diameter (%) | n/a | 99.4±0.3 | 100.2±1.1 | 100.3±1.0 | 100.7±0.4 | 100.6±0.6 |
| Thickness (%) | n/a | 96.2±2.3 | 94.8±2.3 | 95.0±2.2 | 94.7±1.2 | 96.6±2.9 |
| Weight (mg) | n/a | 242.2±3.7 | 245.5±2.3 | 247.5±3.9 | 246.8±2.5 | 245.6±2.7 |
| Density (mg/mm3) | n/a | 1.08±0.02 | 1.09±0.02 | 1.10±0.02 | 1.09±0.01 | 1.07±0.02 |
| Remaining curcumin (%) | n/a | 78.7±7.9 | 74.4±10.3 | 64.4±4.2 | 55.9±3.6 | 53.6±5.6 |
| °C | 200 | 210 | 220 | 230 | 240 | 250 |
| Diameter (%) | 101.9±0.7 | 101.9±0.7 | 103.9±1.3 | 103.4±1.0 | 103.5±0.8 | 104.2±0.9 |
| Thickness (%) | 98.8±2.7 | 101.8±2.5 | 100.8±2.6 | 100.0±1.9 | 96.6±0.5 | 95.7±1.8 |
| Weight (mg) | 246.8±3.0 | 250.9±6.2 | 255.3±3.6 | 253.6±4.9 | 251.8±4.3 | 256.8±3.3 |
| Density (mg/mm3) | 1.02±0.03 | 1.01±0.01 | 1.00±0.03 | 1.01±0.02 | 1.03±0.00 | 1.04±0.04 |
| Remaining curcumin (%) | 46.3± 6.0 | 32.2±2.3 | 30.1±3.1 | 22.9±4.7 | 17.1±1.8 | 14.4±2.7 |
The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions were set by the 3D printing slicer software. Data represent the mean±S.D. (n=5).
Given this color change, we measured the amount of curcumin remaining in the curcumin-loaded PVA tablets (Table 3) and found that it gradually decreased with increasing temperature. These results indicate that curcumin was degraded by the 3D-printing process and that the nozzle temperature can affect drug stability. Increasing the printing speed might prevent this degradation by reducing the exposure time to the heated nozzle. Consistent with these results, Sadia et al. mentioned the color change of tablets as a possibility from degradation of drug (5-ASA) subjected to thermal processes, including hotmelt extrusion and 3D printing.28) The improvement of heating condition and/or device will allow successful 3D product printing in the future.
General Physical Properties of PVA and Curcumin-FilamentsFigure 5A shows the PXRD peak patterns of the two types of filaments. A typical halo pattern was obtained for both PVA and curcumin-loaded PVA filament and no peaks due to curcumin were observed in the latter sample. These results indicate that the minimum loading of curcumin into PVA (1750±230 µg curcumin/g filament) was insufficient to be observed by X-ray diffraction (XRD). Figure 5B shows that PVA and curcumin-loaded PVA provided similar scans and that pure curcumin provided a peak at around 187°C.
Dissolution tests were conducted to evaluate the quality of the PVA-based and curcumin-loaded PVA tablets (Fig. 6) using three diameters (5, 10, 15 mm) of each tablet type. All tablets provided similar results. Skowyra et al. investigated prednisolone-loaded PVA tablets and found that smaller tablets tended to release drug more quickly due to a larger surface area/mass ratio.15) They evaluated the drug dissolution by using flow through cell method against slight bigger size of tablets (the range of diameters, width, and height of tablets were from 8.39, 3.36, 3.36 to 15.50, 6.20, 6.20 cm). These results suggest that different size, different experimental conditions and drugs provide different drug dissolution profiles. The finding that PVA and curcumin-loaded PVA tablets show similar dissolution profiles confirmed that the release of curcumin is linked with the disintegration of PVA. Deviations in the curcumin tablet dissolution data were greater than that for the PVA tablet data. We assume that the heterogenous sampling from PVA–water cluster entrapping or interacting with curcumin might affect the results. Additionally, PVA improves the dissolution of curcumin, which is a poorly water-soluble drug. Sun et al. developed a curcumin-loaded PVA fiber and a curcumin-cyclodextrin inclusion complex-loaded PVA fiber29) and demonstrated the improved dissolution of curcumin as the amount of PVA increased.
(A) PVA tablets. (B) Curcumin-loaded PVA tablets. The thicknesses of all tablets were set to 3 mm. The printing conditions for the 3D printing slicer software were as follows: printing temperature, 160°C; flow rate, 120%; fill density, 100%. Data represent the mean±S.D. (n=3).
An infilled 3D object is frequently prepared to save printing time and cost. In this study, low density floating tablets were prepared. Several different floating tablets and microspheres were reported previously as gastro-retentive drug delivery systems30–32) because such tablets should provide prolonged drug release by floating in the stomach. Tablets can be easily prepared using the current 3D printing system by simply changing the fill density of the interior of the tablet. Infilled tablets were designed (Figs. 7A, B), and cross sectional images of curcumin-loaded PVA tablets with different fill densities were obtained by prematurely stopping the 3D-printing process and are shown in Fig. 7C. A lattice-type structure was introduced to fill the voids in the infilled tablets (look at the tablet with 20 and 40% fill density in Fig. 7C). The design of other inner structures in 3D-printed objects that might change the dissolution profile of the resulting tablets is also possible by using other slicer software. The appearance, mean diameter and mean thickness of all PVA tablets were similar for each fill density (Fig. 7A, Table 4), in contrast, the tablet densities decreased as the fill density was set lower.
(A) Appearance of a 3D printed tablet. (B) Schematic diagram of a tablet. (C) Cross sectional images of tablets. The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions for the 3D printing slicer software were as follows: printing temperature, 160°C; flow rate, 120%.
| % | 0 | 20 | 40 | 60 | 80 | 100 |
|---|---|---|---|---|---|---|
| Diameter (%) | 98.9±0.7 | 99.5±0.5 | 100.1±1.0 | 100.1±1.0 | 99.7±0.9 | 100.4±0.6 |
| Thickness (%) | 96.4±1.2 | 96.2±1.4 | 98.7±4.3 | 96.0±1.9 | 99.0±2.6 | 97.6±2.5 |
| Weight (mg) | 149.9±2.3 | 170.3±3.4 | 190.0±2.4 | 208.1±2.9 | 231.2±3.6 | 250.3±3.9 |
| Density (mg/mm3) | 0.67±0.01 | 0.76±0.02 | 0.82±0.02 | 0.92±0.02 | 1.00±0.02 | 1.08±0.02 |
The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions were set by the 3D printing slicer software. Data represent the mean±S.D. (n=5).
The buoyancies of these 3D printed tablets were evaluated with time (Table 5). Tablets with lower fill density (0, 20, 40, 60%) consistently floated and finally dissolved whereas tablets with a high fill density (100%) and high density (>1.00 mg/mm3) consistently sank. The tablet with 80% fill density initially sank and then started floating, indicating that dissolution of the tablet surface decreased the total density. The dissolution profiles of curcumin from curcumin-loaded PVA tablets with different fill densities are shown in Fig. 8 and tablets with lower fill density showed faster drug dissolution. Goyanes et al. also reported a clear tendency for fast dissolution of infilled 4-aminosalicylic acid-loaded PVA tablets.17) That report partially supports our present results that the experimental conditions and properties of the drug can affect the drug dissolution profile. Multifunctional tablets such as osmotic stress-sensitive tablets33) and tablets exhibiting two independently controlled release profiles34) have been developed recently. Floating tablets may be useful as novel functional tablets.
| Time (min) | 0 | 20 | 40 | 60 | 80 | 100 |
|---|---|---|---|---|---|---|
| 0 | + | + | + | + | − | − |
| 15 | + | + | + | + | ± | − |
| 30 | + | + | + | + | ± | − |
| 60 | × | × | × | × | × | × |
+, floating; ±, up and down; −, sinking, ×, disappeared.
The diameters and thicknesses of all tablets were set to 10 and 3 mm, respectively. The printing conditions for the 3D printing slicer software were as follows: printing temperature, 160°C; flow rate, 120%. Data represent the mean±S.D. (n=3).
In conclusion, we showed that 3D-printing conditions affect the formability of 3D-printed tablets. An FDM-type 3D printer requires a thermal process to extrude the drug-loaded polymer, and control of the extruded amount and the printing temperature is important to produce tablets with the desired properties. Floating tablets were prepared by changing the fill density. This present 3D-printing system can prepare the desired size and shape of tablets on demand and is applicable for the production of multi-functional tablets. Although differences in 3D printers and 3D slicer software can affect the formability of a 3D object, the development of new 3D printers and 3D software compatible with IoT technology will improve the productivity and accuracy of 3D-printed tablets and drugs. 3D-printed tablets hold promise for patient-tailored drugs. The present results will be useful for producing 3D-based tablets and medicines using FDM-type 3D printers.
The authors declare no conflict of interest.
