Abstract
Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.
Highlights
Three-dimensional (3D) printing is a transformative additive manufacturing technology that allows the fabrication of objects from a computer-aided design (CAD) file in a layer-by-layer manner [1]
PEGDA600 and PEG400 were mixed according to the predesigned ratios (Table 1) for 1 h, and TPO was added into the mixture, and the whole solution was stirred for at least 8 h at 25 ◦ C until the TPO was completely dissolved
While further increasing the tartrazine ratio to 0.12% resulted the incomplete curing of photopolymer, leading to the printed pellets having a shorter diameter than the model size
Summary
Three-dimensional (3D) printing is a transformative additive manufacturing technology that allows the fabrication of objects from a computer-aided design (CAD) file in a layer-by-layer manner [1]. 3D printing could potentially create extra benefits in terms of both personalized design and precise fabrication of drug dosages with sophisticated geometries and programmable drug release behaviors, including immediate release [11,12] or modified drug release profiles [13,14,15], some of which may contain multiple drugs [16,17]. The relatively low precision and the discontinuous printing process (the requisite of an additional step for the preparation of the printing filament) of the FDM currently impede its practical applications, those for temperature-sensitive drugs and ingredients [23,24]
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