Additive Manufacturing of Personalized Pharmaceutical Dosage Forms via Stereolithography.

The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.00%, were fabricated via stereolithography (SLA) using a novel photopolymerizable resin formulation based on a monomer mixture that, to date, has not been reported in the literature, with paracetamol and aspirin selected as model drugs. In order to produce the dosage forms, the ratio of poly(ethylene glycol) diacrylate (PEGDA) to poly(caprolactone) triol was varied with diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure TPO) utilized as the photoinitiator. The fabrication of 28 dosages in one print process was possible and the printed dosage forms were characterized for their drug release properties. It was established that both drugs displayed a sustained release over a 24-h period. The physical properties were also investigated, illustrating that SLA affords accurate printing of dosages with some statistically significant differences observed from the targeted dimensional range, indicating an area for future process improvement. The work presented in this paper demonstrates that SLA has the ability to produce small, individualized batches which may be tailored to meet patients' specific needs or provide for the localized production of pharmaceutical dosage forms.

Influence of Annealing and Biaxial Expansion on the Properties of Poly(l-Lactic Acid) Medical Tubing.

Poly-l-lactic acid (PLLA) is one of the most common bioabsorbable materials in the medical device field. However, its use in load-bearing applications is limited due to its inferior mechanical properties when compared to many of the competing metal-based permanent and bioabsorbable materials. The objective of this study was to directly compare the influence of both annealing and biaxial expansion processes to improve the material properties of PLLA. Results showed that both annealing and biaxial expansion led to an overall increase in crystallinity and that the crystallites formed during both processes were in the α' and α forms. 2D-WAXS patterns showed that the preferred orientation of crystallites formed during annealing was parallel to the circumferential direction. While biaxial expansion resulted in orientation in both axial and circumferential directions, with relatively equal sized crystals in both directions, Da (112 Å) and Dc (97 Å). The expansion process had the most profound effect on mechanical performance, with a 65% increase in Young's modulus, a 45% increase in maximum tensile stress and an 18-fold increase in strain at maximum load. These results indicate that biaxially expanding PLLA at a temperature above Tcc is possible, due to the high strain rates associated with stretch blow moulding.

The Influence of Low Shear Microbore Extrusion on the Properties of High Molecular Weight Poly(l-Lactic Acid) for Medical Tubing Applications.

Biodegradable polymers play a crucial role in the medical device field, with a broad range of applications such as suturing, drug delivery, tissue engineering, scaffolding, orthopaedics, and fixation devices. Poly-l-lactic acid (PLLA) is one of the most commonly used and investigated biodegradable polymers. The objective of this study was to determine the influence low shear microbore extrusion exerts on the properties of high molecular weight PLLA for medical tubing applications. Results showed that even at low shear rates there was a considerable reduction in molecular weight (Mn = 7-18%) during processing, with a further loss (Mn 11%) associated with resin drying. An increase in melt residence time from ~4 mins to ~6 mins, translated into a 12% greater reduction in molecular weight. The degradation mechanism was determined to be thermal and resulted in a ~22-fold increase in residual monomer. The differences in molecular weight between both batches had no effect on the materials thermal or morphological properties. However, it did affect its mechanical properties, with a significant impact on tensile strength and modulus. Interestingly there was no effect on the elongational proprieties of the tubing. There was also an observed temperature-dependence of mechanical properties below the glass transition temperature.

Comparison of fused-filament fabrication to direct compression and injection molding in the manufacture of oral tablets.

Oral tablets are a convenient form to deliver active pharmaceutical ingredients (API) and have a high level of acceptance from clinicians and patients. There is a wide range of excipients available for the fabrication of tablets thereby offering a versatile platform for the delivery of therapeutic agents to the gastrointestinal tract. However, the geometry of tablets is limited by conventional manufacturing processes. This study aimed to compare three manufacturing processes in the production of flat-faced oral tablets using the same formulation composed of a polymer blend and caffeine as a model drug: fused-filament fabrication (FFF), direct compression (DC) and injection molding (IM). Hot-melt extrusion was used to convert a powder blend into feedstock material for FFF and IM processes, while DC was performed on the powder mixture. Tablets were produced with the same dimensions and were characterized for their physical and dissolution properties. There were statistical differences in the physical properties and drug release profiles of the tablets produced by the different manufacturing processes. DC tablets displayed immediate release, IM provided sustained release over 48 h, and FFF tablets displayed both release types depending on the printing parameters. FFF continues to demonstrate high potential as a manufacturing process for the efficient production of personalized oral tablets.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms.

Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more) of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.