ABSTRACT
This study aims to establish the design space of the key processes for drop-on-powder 3D printing based on design of experiment (DoE). By utilizing Minitab, an experimental scheme with three factors, two levels and three center points was designed to analyze the factors that significantly affected the tablet quality attributes. Furthermore, the factor interactions were analyzed using Minitab. subsequently, the computer aided drafting (CAD) software was used to adjust the model volume with fixed radius/height ratio (r/h = 1.25) and establish a linear regression equation between model volume and dose. As a result, the drug dose could be controlled in a flexible manner. The finally determined process parameters were: ink-jet level is 12, layer thickness is 150 μm, and the X-axis printing head speed of 635 mm·s-1. Regression equation between drug content (y) and model volume (x) was y = 0.062 x - 0.582 7 (R2 = 0.999 9) showing good linear relationship. This indicated that robust and feasible process parameters were obtained through DoE, and the preparation of personalized-dose tablets was realized with good reproducibility.
ABSTRACT
Objective: To prepare acetaminophen tablets by hot-melt extrusion 3D printing technique. Methods:The acetaminophen tablets were prepared by the direct combination of hot-melt extrusion technology and 3D printing. Soluplus was used as hot-melt matrix and PEG6000 as plasticizer. The physical properties and molecular structure of the materials in the tablets were investigated, and in vitro release of the tablets was studied. Results:The printing of acetaminophen tablets was completed successfully, and the size, internal structure and shape of the tablets could be changed by 3D printing technology. The thermogravimetric analysis showed that all materials could maintain thermal stability at printing temperature. The results of crystal form study showed that all materials solidified in a amorphous form after the hot-melt 3D printing. The IR, Raman, MS and 1 H NMR data showed that the molecular structure of acetaminophen kept unchanged after the 3D printing. The in vitro release studies showed that the release of printed tablets could achieve over 80% within 24 h in the pH 6.8 phosphate buffer medium, by adding the disintegrating agent, kolidon cl-F, and changing the path spacing and shell numbers in the printing process. Conclusion:The acetaminophen tablets could be prepared by the hot-melt extrusion 3D printing technology, and the release of the tablets could be adjusted by the change of printing-related parameters.
ABSTRACT
The aim of this study is to prepare acetaminophen sustained-release tablets by hot melt extrusion 3D printing technology based on the concept of "Quality by Design" (QbD). Firstly, the failure mode and effect analysis (FMEA) was used to determine the critical process parameters (CPPs), then full-factor experimental design was used to analyze the critical quality attributes (CQAs) and to establish the design space. The results showed that the content of plasticizer, the path spacing and the shell numbers are independent variable for the experimental design. The design space was concluded to be plasticizer content: 9%, and the shell number: 3-5, the path spacing: 1.05-1.2 mm. In this study, 3D printing technology was used to prepare acetaminophen sustained-release tablets in accordance with the concept of QbD, which improved the durability of the process and ensured the uniform and controllable quality of the preparation and also provided experimental basis for personalised medicine.
ABSTRACT
Background Retinal development continues during the early postnatal period in mammals.Correct arrangement of layers and precise location of various cells in the retina are vital for forming normal visual function during critical period plasticity.Spectral-domain optical coherence tomography(SD-OCT)provides highquality in vivo retinal imaging and the possibility to measure retinal thickness longitudinally. Objective The present study was to investigate the changes of retinal thickness during critical period plasticity in rats. Methods In vivo consecutive scanning of retinal image was performed in 10 SPF Sprague-Dawley rats at postnatal day 14(P14),P18,P21,P24 and P42 with SD-OCT,and retinal histopathological examination was used to detect retinal morphologic changes at the same postnatal ages in 20 matched rats.The whole retinal thickness,the thickness from inner limiting membrane(ILM)to inner plexiform layer(IPL),the thickness of inner nuclear layer(INL)and the thickness from outer nuclear layer(ONL)to retinal pigment epithelium(RPE)were measured using Cirrus HD-OCT system and HMIAS-2000 Imaging System in retinal sections.The measurement parameters by Cirrus HD-OCT and those by hematoxylin-eosin staining were compared.The use of animals followed the Statement of National Institute of Health (USA). Results In vivo high-resolution images of rat retinas with SD-OCT compared well with histology,which enabled quantitative comparison of the SD-OCT and histological data during critical period plasticity in rats.From P14 to P42,the retinal thickness gradually decreased with the increase of rat ages(F=15.425,P=0.000),and so were the thickness from ILM to IPL,the thickness of INL and the thickness from ONL to RPE(F=3.973,P=0.007;F=17.529,P=0.000;F=7.038,P=0.000).The retinal thickness,thickness of INL.thickness from ONL to RPE measured by Cirrus HD-OCT were significantly correlated with those measured by retinal sections among P14,P18,P21,P24 and P42 rats(r=0.794,P=0.000;r=0.784,P=0.000;r=0.681,P=0.000). Conclusion SD-OCT is a demonstratably valuable technology to study the structure of retinas in rats.The retinal thickness is shown to reduce in thickness throughout the development of the retina during critical period plasticity due to the decrease in thickness of INL and the distance from the ONL to RPE,as illustrated by OCT scanning.