Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry

Abstract

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.

Development of Bio-Active Patches Based on Pectin for the Treatment of Ulcers and Wounds Using 3D-Bioprinting Technology

“…A key factor that influences the extent of dispersion of CCP in the film matrix, and consequently the opacity of the films, is the interaction between pectin and chitosan (present in CCP). The different charges of pectin and chitosan lead to the formation of ionic bonds that directly result in the topical cross-linking of pectin around CCP [14], thus inhibiting extended dispersion of the later. This topical cross-linking can elucidate the presence of the larger coagulants that were visible in the films.…”

“…Figure 4, summarizes the ATR-FTIR spectra of the patches, the spectra of their composites with CCP, and the spectra of CCP. The spectra in Figure 7 revealed a broad band around 3700-3000 cm −1 for all films and for CCP, typical for polysaccharides, attributed to the O-H stretching vibration (OH), while peaks around 3000-2800 cm −1 were attributed to C-H stretching vibrations (νCH) [14]. Regarding the spectrum of pectin films, two bands were detected between 1800-1500 cm −1 , which were attributed to the stretching vibrations of the carbonyl group (νC=O) [14].…”

“…The spectra in Figure 7 revealed a broad band around 3700-3000 cm −1 for all films and for CCP, typical for polysaccharides, attributed to the O-H stretching vibration (OH), while peaks around 3000-2800 cm −1 were attributed to C-H stretching vibrations (νCH) [14]. Regarding the spectrum of pectin films, two bands were detected between 1800-1500 cm −1 , which were attributed to the stretching vibrations of the carbonyl group (νC=O) [14]. The band located at 1733 cm −1 corresponds to the νC=O of the methyl ester group (COOCH 3 ) and to the non-dissociated carboxyl group (COOH), while the band located at 1624 cm −1 is assigned to the asymmetric stretching vibration of the carbonyl group of the carboxyl ion (COO-) [14].…”

“…Regarding the spectrum of pectin films, two bands were detected between 1800-1500 cm −1 , which were attributed to the stretching vibrations of the carbonyl group (νC=O) [14]. The band located at 1733 cm −1 corresponds to the νC=O of the methyl ester group (COOCH 3 ) and to the non-dissociated carboxyl group (COOH), while the band located at 1624 cm −1 is assigned to the asymmetric stretching vibration of the carbonyl group of the carboxyl ion (COO-) [14]. The CCP spectrum revealed a band centered at 1647 cm −1 , attributed to the νC=O of the amide group (also known as Amide I band) of the acetylated units of chitosan, present in the CCP.…”

How innovative drug delivery devices can help realize clinical utility of new effective therapies

“…3DP technology offers a novel manufacturing platform for direct fabrication of individual dosage forms (e.g. multidrug implants, tablets) and has the potential to allow variations in their size and geometry, as well as to control dose and release behavior [2]. Furthermore, the low cost and ease of use of 3DP systems mean that the possibility of manufacturing medicines and medical devices at the point of dispensing or the point of use could become a reality [3].…”