3D Printing of Dapagliflozin Containing Self-Nanoemulsifying Tablets: Formulation Design and In Vitro Characterization

Abstract

The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. A self-nanoemulsifying tablet formulation of dapagliflozin propanediol monohydrate was developed utilizing the semisolid pressure-assisted microsyringe (PAM) extrusion-based 3D printing technique. The developed formulation system consists of two major components (liquid and solid phase), which include oils (caproyl 90, octanoic acid) and co-surfactant (PEG 400) as liquid phase while surfactant (poloxamer 188) and solid matrix (PEG 6000) as solid-phase excipients that ultimately self-nanoemulsify as a drug encapsulated nanoemulsion system on contact with aqueous phase/gastrointestinal fluid. The droplet size distribution of the generated nanoemulsion from a self-nanoemulsifying 3D printed tablet was observed to be 104.7 ± 3.36 nm with polydispersity index 0.063 ± 0.024. The FT-IR analysis of the printed tablet revealed that no drug-excipients interactions were observed. The DSC and X-RD analysis of the printed tablet revealed that the loaded drug is molecularly dispersed in the crystal lattice of the tablet solid matrix and remains solubilized in the liquid phase of the printed tablet. SEM image of the drug-loaded self-nanoemulsifying tablets revealed that dapagliflozin propanediol monohydrate was completely encapsulated in the solid matrix of the printed tablet, which was further confirmed by SEM-EDS analysis. The in vitro dissolution profile of dapagliflozin-loaded self-nanoemulsifying tablet revealed an immediate-release drug profile for all three sizes (8 mm, 10 mm, and 12 mm) tablets, exhibiting >75.0% drug release within 20 min. Thus, this study has emphasized the capability of the PAM-based 3D printing technique to print a self-nanoemulsifying tablet dosage form with an immediate-release drug profile for poorly water-soluble drug.

3D Printing of Thermo-Sensitive Drugs

“…Furthermore, several other studies reported the use of SSE printing techniques to fabricate tablets [ 51 , 68 , 69 , 70 , 71 ], oral films [ 72 ], and scaffolds [ 73 ], illustrating that SSE is an excellent technique to fabricate thermosensitive drugs at a lower temperature.…”

“…It is worth noting that coaxial SSE 3DP, where the coaxial extruder fixed to the printhead of the Ultimaker3 printer was connected through tubes to the syringe pump system, was used for the fabrication of propranolol-loaded drug delivery system [67]. Furthermore, several other studies reported the use of SSE printing techniques to fabricate tablets [51,[68][69][70][71], oral films [72], and scaffolds [73], illustrating that SSE is an excellent technique to fabricate thermosensitive drugs at a lower temperature.…”

Three-Dimensional Printing of a Container Tablet: A New Paradigm for Multi-Drug-Containing Bioactive Self-Nanoemulsifying Drug-Delivery Systems (Bio-SNEDDSs)

“…The objects were printed using an FDM 3D printer (Ultimaker S3, Utrecht, The Netherlands) at a temperature of 150 °C at a print speed of 50 mm/s. The bed temperature was kept at 80 °C and a 0.4 mm BB4 print head was used for the process [ 22 , 23 , 24 ]. The printing temperature was selected based on the preliminary thermal analysis, to ensure that the contents of our product to be filled in are not degraded by the heat of the nozzle.…”

“…More studies need to be conducted to explore the incorporation of SNEDDSs into 3D-printed tablets [ 22 , 23 , 24 ]. In the current study, we report the incorporation of the pre-formulated SNEDDSs into 3D-printed-container systems, for the delivery of two different drugs with inherent poor solubility, namely, curcumin (CUR) and lansoprazole (LNS).…”

Personalised Tasted Masked Chewable 3D Printed Fruit-Chews for Paediatric Patients

“…Nevertheless, 3D printing has been studied systematically for the optimisation of 3D printed tablets [ 9 ] using a variety of technologies and materials (e.g., polymers, resins, hydrogels). The selection of the technology is usually related to the drug product specifications and such as water solubility, thermal stability, active dose and drug-excipient miscibility [ 10 , 11 ]. Selective laser sintering (SLS) was used by Awad et al to develop fast dissolving tablets of paracetamol for visually impaired patients.…”