Characterization of Inks for 3D Printing of Ivermectin Tablets

SANTIAGO N. CAMPOS; CINTIA A. BRIONES NIEVAS; ELIO E. GONZO; ALICIA G. CID; JOSÉ M. BERMUDEZ; ANALÍA I. ROMERO; MERCEDES VILLEGAS

Rosario

Congreso; Reunión Internacional de Ciencias Farmacéuticas; 2023

3D printing of pharmaceutical forms from semisolid inks is an emerging technology with great potential in the pharmaceutical area. The aim of the work was to determine the physicochemical and drug release properties of ivermectin semisolid inks to optimize their performance for further use in 3D printing technology. Inks based on Gelucire 50/13 (GC), Poloxamer 188 (P188), Poloxamer 407 (P407) and Soluplus (SP), loaded with 10 % w/w Ivermectin (IVM) were evaluated. The compositions of the inks from which molded tablets were obtained were 90 % w/w GC; 45 % w/w GC + 45 % w/w P188 (GC-P188); 45 % w/w GC + 45 % w/w P407 (GC-P407); 81 % w/w GC + 9 % w/w SP (GC-SP). Scanning electron microscopy (SEM) and rheology tests were carried out to characterize the structure and rheological behavior of the inks. To perform in vitro IVM release tests, the inks were molded in oblong-shaped molds to obtain tablets, which were evaluated in a dissolution test for 3 h using HCl at 37°C as medium. Rheological testing of the inks included analysis of the viscosity profile as a function of shear rate, recovery test and temperature sweep to determine the glass transition temperature (Tg). On the other hand, the total amount of IVM available for dissolution (M∞) in the moldings after 24 h of dissolution in HCl was determined.SEM images showed all the inks obtained presented a single homogeneous phase without the presence of IVM crystals. All the inks showed a shear thinning behavior (when stress is applied, their fluidity increases), typical of polymer-based materials used in 3D printing. From the temperature sweep, Tg was determined by crossover of the G´ and G´´ moduli at 53.4, 51.9, 50.5 and 45.9 °C for GC, GC-P188, GC-P407 and GC-SP, respectively. The Tg value allows estimating the appropriate temperature for printing. Regarding the recovery test, GC-SP ink was able to obtain a higher recovery, 117 %, after the application of a large deformation. This value indicates that the ink is able to recover its initial viscosity after printing, improving the stability of the print layer by layer, and consequently the final quality of the print. The dissolution tests showed different profiles depending on the combination of polymers used. These were adjusted with the Lumped-Gonzo mathematical model, except for the molding obtained only with GC, which was adjusted with a dual model, consisting of the Lumped-Gonzo model (up to 60 min) and the Korsmeyer-Peppas model (from 60 to 180 min). Mean dissolution time (MDT) was calculated from these models. GC (84.14 min) and GC-SP (58.22 min) inks presented the highest values for MDT, which would indicate that the release of IVM from these inks is slower. However, the maximum dissolved mass of IVM was presented by the GC-SP ink (57.21 mg), indicating that the presence of this combination of polymers favors drug solubility. This could lead to a subsequent increase in bioavailability. The results of this work show that the evaluated inks are promising for 3D printing of ivermectin floating tablets, with good rheological behavior, good structural integrity and adequate IVM release profiles. However, the use of other excipients or excipient combinations will continue to be evaluated to improve ink properties such as melt flow index and glass transition temperature.