Abstract-A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging

Anna Novikova, Daniel Markl, J. Axel Zeitler, Thomas Rades, Claudia S.Leopold

http://www.sciencedirect.com/science/article/pii/S0928098717305845


Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets were imaged by TPI and the results were compared to X-ray microtomography. The terahertz pulse beam propagates through the tablets and is back-reflected at the interface between the MCC matrix and the coated pellets within the tablet causing a peak in the terahertz waveform. Cross-section images of the tablets were extracted at different depths and parallel to the tablet faces from 3D terahertz data to visualise the surface-near structure of the MUPS tablets. The images of the surface-near structure of the MUPS tablets were compared to X-ray microtomography images at the same depths. The surface-near structure could be clearly resolved by TPI at depths between 24 and 152 μm below the tablet surface. An increasing amount of pellets within the MUPS tablets appears to slightly decrease the detectability of the pellets within the tablets by TPI. TPI was shown to be a non-destructive method for the detection of pellets within the tablets and could resolve structures thicker than 30 μm. In conclusion, a proof-of-concept was provided for TPI as a method of quality control for MUPS tablets.

Abstract-Multispectral UV imaging for determination of the tablet coating thickness

• Anna Novikova^a, 
• Jens M. Carstensen^b, 
• J. Axel Zeitler^c, 
• Thomas Rades^d, 
• Claudia S. Leopold^a, , 

• ^a Division of Pharmaceutical Technology, Department of Chemistry, University of Hamburg, Bundesstraße 45, 20146 Hamburg, Germany
• ^b Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads Building 321, 2800 Lyngby, Denmark
• ^c Department of Chemical Engineering, University of Cambridge, New Museums Site, Pembroke Street, Cambridge, CB2 3RA, United Kingdom
• ^d Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark

http://www.sciencedirect.com/science/article/pii/S0022354917300886

The applicability of off-line multispectral ultraviolet (UV) imaging in combination with multivariate data analysis was investigated to determine the coating thickness and its distribution on the tablet surface during lab scale coating. The UV imaging results were compared with the weight gain measured for each individual tablet and the corresponding coating thickness and its distribution measured by terahertz pulsed imaging (TPI). Three different tablet formulations were investigated, two of which contained UV active tablet cores. Three coating formulations were applied: Aquacoat^®ECD (a mainly translucent coating) and Eudragit^® NE (a turbid coating containing solid particles). It was shown that UV imaging is a fast and non-destructive method to predict individual tablet weight gain as well as coating thickness. The coating thickness distribution profiles determined by UV imaging correlated to the results of the TPI measurements. UV imaging appears to hold a significant potential as a PAT tool for determination of the tablet coating thickness and its distribution resulting from its high measurement speed, high molar absorptivity and a high scattering coefficient, in addition to relatively low costs.

Abstract-Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging

• Daniel Markl, 
• J. Axel Zeitler, 
• Cecilie Rasch, 
• Maria Høtoft Michaelsen, 
• Anette Müllertz, 
• Jukka Rantanen, 
• Thomas Rades, 
• Johan Bøtke, 
• http://link.springer.com/article/10.1007/s11095-016-2083-1

Purpose

A 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).

Methods

Printing was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.

Results

A clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3).

Conclusions

The 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms