@conference{
author = "Krkobabić, Mirjana and Pešić, Nikola and Boljević, Gordana and Medarević, Đorđe and Ibrić, Svetlana",
year = "2021",
abstract = "INTRODUCTION
Application of the 3D printing in pharmacy make possible production of small batches of solid dosage forms for oral administration (printlets) with different dose and release characteristics that can be customized to specific patient needs [1]. Digital light processing (DLP), one type of 3D printing technology, is based on a UV-triggered localized photopolymerization process of liquid resins [2]. The aim of this study was 3D printing from photoreactive dispersions with different amounts of solid phase and characterization of obtained printlets.
MATERIALS
Different photoreactive dispersions were prepared from poly(ethylene glycol) diacrylate 700 (PEGDA 700, Sigma-Aldrich, Japan), poly(ethylene glycol) 400 (PEG 400, Fagron, Netherlands), atomoxetine (kindly provided by Hemofarm AD, Vrsac, Serbia), diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (DPPO, Sigma-Aldrich, Germany).
Preparation of photoreactive dispersions
Atomoxetine was used as an active ingredient, while PEGDA was used as a photopolymer and DPPO as a photoinitiator in photoreactive dispersions. PEG 400 was used as an excipient to overcome very slow and incomplete drug release from printlets fabricated by photopolymerization using DLP technology. The ratio of PEGDA and PEG 400 was constant in all formulations (3:1), and content of atomoxetine was varied from 5% to 27.5% (Table 1). 30 g of each formulation was prepared by mixing on the magnetic stirrer for 15 minutes, protected from the light.
3D printing of atomoxetine printlets
The templates used for printlets were designed by Autodesk Fusion 360 software and exported as a stereolithography file (.stl) into Creation Workshop X 1.2.1 software. All printlets were fabricated using DLP printer Duplicator 7 (Wanhao, Zhejiang, China). The selected shape was cylinder (8 mm diameter and 2 mm height). Printlets containing 5.00% of atomoxetine were printed with exposure time 5 s, while printlets containing 12.50%, 20.00%, and 27.50% were printed with exposure time 10 s because it was not possible to print more than 1 printlet with exposure time 5 s. All printlets were fabricated without bottom layers, and with layer thickness 0.1 mm.
Determination of mass, dimension and tensile strength of printlets
Mass was determined on 20 printlets, and dimension (digital caliper, Vogel, Germany) was determined on 10 printlets for each formulation. Tensile strength of all formulations was calculated according to the following equation [3]:
σx=2F/πDt
Where:
σx is the tensile strength; F is the tablet breaking force (load); D and t are the diameter and thickness of printlets, respectively.
In vitro drug release testing
Atomoxetine dissolution rate from 3D printlets was tested using USP IV (Flow-through cell, CE7 smart, Sotax, Switzerland) apparatus. Three printlets of each formulation were tested in 250 ml of distilled water at 37±0.5 °C, with a flow rate of 8 ml per minute during 8 h. The amount of dissolved atomoxetine was determined by UV/VIS spectrophotometry at 270 nm (Evolution 300, Thermo Fisher Scientific, Cambridge).
RESULTS AND DISCUSSION
3D printing process
Printlets containing four different amounts of atomoxetine were successfully produced using photoreactive dispersions by the DLP printer. Achieved doses of atomoxetine in printlets were 5.84±0.54 mg, 20.24±0.82 mg, 32.46±1.69 mg and 58.08±3.09 mg, which is a wide range of doses that allow personalization of therapy. Also, total printing time for 10 printlets was 5 and 7 minutes, for exposition time 5 s and 10 s, respectively, which is significantly shorter than printing time in other 3D printing technologies.
Mass, dimension and tensile strength of printlets
Mass, diameter and thickness are shown in Table 2, while tensile strengths of all formulations are shown in Figure 1.
The increase in the atomoxetine content led to the fabrication of printlets with a higher mass and dimensions, due to the higher proportion of atomoxetine particles that were not dissolved in photoreactive mixture and their scattering phenomena in the light beam.
Increasing content of active ingredient led to higher tensile strength of printlets, and all formulations had tensile strength around 1 MPa, which can be sufficient for small batches [4].
Dissolution profiles
Dissolution profiles of formulations containing different content of atomoxetine are shown in Figure 2. Only from formulation A1 more than 80% of atomoxetine was released after 2 h, which can be a consequence of shorter exposition time set during the printing for this formulation, while formulations A2-A4 overlapped during the first hour of the test and achieved sustained release during 8h. After 8h, 88.94%, 79.77%, 77.53% and 72.54% of atomoxetine were released from formulations A1, A2, A3, and A4, respectively.
CONCLUSION
The possibility of successful 3D DLP printing of the printlets using the active ingredient dispersed in the photopolymer mixture, with optimization of printing process parameters for rapid printlet production, has been demonstrated. Printlets with higher content of dispersed atomoxetine have shown decreased drug release rate after 8h, with increasing tensile strength, mass, and dimensions, due to interactions with the light beam.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting",
title = "Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology",
pages = "1-2",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5325"
}
