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

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.

3D extrusion printing of high drug loading immediate release paracetamol tablets.

The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards.

3D printing of tablets using inkjet with UV photoinitiation.

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector.

Cell clarification and size separation using continuous countercurrent magnetophoresis.

Nonmagnetic microparticles (e.g., cells, polymer beads) immersed in a magnetic fluid (ferrofluid) under a nonuniform magnetic field experience a magnetophoretic force in the direction of decreasing magnetic field strength. This phenomenon was exploited in the development of a continuous magnetophoretic countercurrent separation for the removal and concentration of micron-sized particles from aqueous suspensions, and in particular as a viable approach for cell clarification of raw fermentation broth. A magnetic fluid is added to the cell suspension, the mixture is introduced to the magnetic separator, which consists of an open flow tube passing between pairs of magnets that move in a direction counter to the flow of the suspension. The cells are pushed ahead of the magnet pairs owing to the magnetophoretic forces acting on them, collected in a tube upstream of the feed injection point, and removed as a concentrated suspension for further treatment.

Polyelectrolyte multilayer films of different charge density copolymers with synergistic nonelectrostatic interactions prepared by the layer-by-layer technique.

Random copolymers composed of diallyldimethylammonium chloride (DADMAC) and acrylamide with varying contents (8-100 mol %) of the cationic DADMAC component were alternated with polyanionic, fully charged poly(styrenesulfonate) to form multilayer thin films. UV-vis spectrophotometry, FTIR spectroscopy, and quartz-crystal microgravimetry (QCM) were employed to follow multilayer buildup. Atomic force microscopy was used to obtain structural information. Layer thicknesses have been determined with small-angle X-ray scattering and ellipsometry, in addition to values calculated from QCM. While in previous work, a critical charge density limit could be observed, below which no layer growth is possible; in this system, multilayer formation takes place with copolymers with charge densities as low as 8 mol %. Instead of a continuous increase of adsorbed amounts with decreasing charge density above the critical charge density, as found in previous work, similar layer thicknesses for films with 100 and 8 mol % charged polyelectrolytes and maximally adsorbed amounts for copolymers in an intermediate charge density region have been found. This adsorption behavior is explained in terms of synergistic nonelectrostatic interactions between the polyelectrolytes used.