3D-Printed Fast-Dissolving Oral Dosage Forms via Fused Deposition Modeling Based on Sugar Alcohol and Poly(Vinyl Alcohol)-Preparation, Drug Release Studies and In Vivo Oral Absorption

Abstract

Three-dimensional printing technology holds marked promise for the pharmaceutical industry and is now under intense investigation. Most research is aimed at a greater efficiency in printing oral dosage forms using powder bed printing or fused deposition modeling (FDM). Oral dosage forms printed by FDM tend to be hard objects, which reduce the risk of cracking and chipping. However, one challenge in printing oral dosage forms via FDM is achieving rapid drug release, because the materials for FDM are basically thermoplastic polymers with slow drug release properties. In this study, we investigated printing a fast-dissolving oral dosage form by adding sugar alcohol to a poly(vinyl alcohol)-based formulation for FDM. Filaments which contain sugar alcohol were successfully prepared, and objects were printed with them as oral dosage forms by FDM. On drug release testing, a printed oral dosage form in a ring shape which contained 55% maltitol showed a more than 85% drug release in 15 min. In vivo oral absorption of this printed oral dosage form in dogs was comparable to that of a conventional fast-dissolving tablet. Of particular interest, the drug release profile and drug amount of the oral dosage forms can be easily controlled by a change in shape using 3D Computer Aided Design. These characteristics will encourage the prevalence of FDM by the pharmaceutical industry, and contribute to the promotion of personalized medicine.

Keywords: PVA; fast dissolving; filament formulation; fused deposition modeling; printed medicine; sugar alcohol.

Figure 1

3D CAD design of a cylindrical shape (12 mm diameter and 1.5 mm height), (a) perspective view and (b) top view. (c) Drug release profiles of the oral dosage form printed using PVA-based filament not containing maltitol (●) and filament containing maltitol(■). Data represent mean ± range, n = 2.

Figure 2

3D CAD design of ring shape (diameter of the outer circle is 12 mm, diameter of the inner circle is 7.6 mm, and 2.5 mm height), (a) perspective view and (b) top view. (c) Drug release profiles of the 3D-printed oral dosage form in the cylindrical shape (●) and ring shape (■). Data of the cylindrical shape represent the mean ± range, n = 2; data of the ring shape represent the mean ± SD, n = 3.

Figure 2

3D CAD design of ring shape (diameter of the outer circle is 12 mm, diameter of the inner circle is 7.6 mm, and 2.5 mm height), (a) perspective view and (b) top view. (c) Drug release profiles of the 3D-printed oral dosage form in the cylindrical shape (●) and ring shape (■). Data of the cylindrical shape represent the mean ± range, n = 2; data of the ring shape represent the mean ± SD, n = 3.

Figure 3

(a) Appearance of filament containing each sugar alcohol. (b) Drug release profiles of 3D-printed oral dosage forms in a ring shape, which printed with filament containing the respective sugar alcohol. Data represent mean ± SD, n = 3.

Figure 4

Complex viscosity (|η*|) data of each powder mixture; PVA only (●), maltitol/PVA/TEC = 35/60/5 (■), lactitol/PVA/TEC = 35/60/5 (▲) and sorbitol/PVA/TEC = 35/60/5 (▼).

Figure 5

(a) Appearance of 3D-printed oral dosage form in a ring shape using a filament containing 55% of maltitol. (b) Drug release profiles of 3D-printed oral dosage form in a ring shape using a filament containing 20% (●), 35% (■) and 55% (▲) of maltitol. Data represent mean ± SD, n = 3.

Figure 6

(a) Appearance of the 3D-printed oral dosage forms (left) and conventional tablets (right). (b) Drug release profiles of the 100 mg 3D-printed oral dosage form (●) and conventional tablet (■). Data represent mean ± range, n = 2.

Figure 7

Plasma drug concentrations after oral administration of the conventional tablet (●) and 3D-printed oral dosage form (■) to beagle dogs. Data represent mean ± SD, n = 4.