Multivariate Design of 3D Printed Immediate-Release Tablets with Liquid Crystal-Forming Drug—Itraconazole

Abstract

The simplicity of object shape and composition modification make additive manufacturing a great option for customized dosage form production. To achieve this goal, the correlation between structural and functional attributes of the printed objects needs to be analyzed. So far, it has not been deeply investigated in 3D printing-related papers. The aim of our study was to modify the functionalities of printed tablets containing liquid crystal-forming drug itraconazole by introducing polyvinylpyrrolidone-based polymers into the filament-forming matrices composed predominantly of poly(vinyl alcohol). The effect of the molecular reorganization of the drug and improved tablets’ disintegration was analyzed in terms of itraconazole dissolution. Micro-computed tomography was applied to analyze how the design of a printed object (in this case, a degree of an infill) affects its reproducibility during printing. It was also used to analyze the structure of the printed dosage forms. The results indicated that the improved disintegration obtained due to the use of Kollidon®CL-M was more beneficial for the dissolution of itraconazole than the molecular rearrangement and liquid crystal phase transitions. The lower infill density favored faster dissolution of the drug from printed tablets. However, it negatively affected the reproducibility of the 3D printed object.

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

“…In contrast to the traditional production of tablets, consisting mainly of pressing a mixture of powders or granules, the relatively high temperature of HME and FDM processes can significantly affect the properties of the formulation ingredients. It can lead to physicochemical changes of the active substance, causing its amorphization [ 10 , 13 , 22 ] or formation of liquid crystals [ 23 ], which can improve the drug dissolution rate. However, it is also related to a significant limitation of the application of fused deposition modeling because the formulation cannot contain thermolabile substances.…”

“…To minimize the exposure of the drug substance to high temperatures during the processes, polymers with low glass transition temperatures can be used as filament-forming substances [ 24 ]. A wide range of thermoplastic polymers can be used as filament-forming pharmaceutical-grade matrices including water-soluble polymers [ 18 , 20 , 23 ], pH-independent retarding agents [ 25 , 26 ], pH-responsive polymers [ 16 , 20 , 25 ], and others. The properties of the polymer, and in particular its water solubility, significantly affect the drug dissolution rate.…”

“…The challenge is also to adjust the conditions of the HME process to prepare high-quality printable filaments, which affects the homogeneity of the printed dosage forms [ 29 ]. In our previous work, we showed the effectiveness of a 4% addition of crospovidone to accelerate the release of itraconazole from 3DP formulations [ 23 ]. Tablets containing superdisintegrants were also printed by Than and Titapiwatanakun.…”

Special Issue: Advanced Materials in Drug Release and Drug Delivery Systems

“…The next three papers are devoted to the ever-expanding technological approaches in solid oral dosage forms like tablets [ 7 , 8 ] and capsules [ 9 ]. Jamróz et al focus on the deep analysis of the relationship between structure and pharmaceutical characteristics in 3D printed tablets.…”

“…To evaluate the influence of a degree of infill on the printing reproducibility and to analyze the tablet structure, micro-computed tomography was used. Authors developed 3D printed immediate release tablets with liquid crystal-forming itraconazole and indicated that optimal tablet characteristics (reproducibility during printing, optimal drug release) was assured when filament formulation of 20% itraconazole, 76% polyvinyl alcohol, and 4% crospovidone was utilized [ 7 ]. Supercritical fluid method is a relatively new technique with potential application in the pharmaceutical industry to reduce particle size and to create inclusion complexes or solid dispersions.…”