Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets

Abstract

Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach.

Development of 3D Printed Tablets by Fused Deposition Modeling Using Polyvinyl Alcohol as Polymeric Matrix for Rapid Drug Release

“…They include incorporation of highly water-soluble materials in formulations, 16,17,22 increasing porosity by reducing infill in 3D printed tablets, 12 and changing geometry of tablets or forming channels into tablets for relatively rapid fragmentation of tablets. 23,24 However, the success of these techniques to increase drug release rate from tablets was mixed and variable. In the present investigation, we have studied the use of a water-soluble polymeric carrier, polyvinyl alcohol (PVA), for its potential effects in enhancing dissolution rates of 3D printed tablets.…”

Fabrication of Muco-Adhesive Oral Films by the 3D Printing of Hydroxypropyl Methylcellulose-Based Catechin-Loaded Formulations

“…11,12) Additionally, tablets with unique designs and geometries prepared by 3D printing allow controlled drug release. [13][14][15][16] Polypills and novel tablets manufactured using a 3D printer may allow personalized dosing, an important advancement since each patient has unique pharmacokinetics and metabolism. The use of 3D printers for preparing pharmaceutical doses may change both drug manufacturing and therapeutic approaches.…”

An Investigation through the Pharmacotechnical Factors-to Develop a Method to Replace a Super Disintegrant in an Immediate Release Tablet

“…At this particular Binder level, to decrease the compressibility index the particle size must be increased the reason behind this phenomenon might be the granules prepared with the higher concentration of binder might be more rigid and harder than those prepared with lower BC. 15 The granules with lower BC is fragile, 16 also during the studies, it breaks down into fine particles or fine powders. 17 Whereas at Higher BC as the granules are harder thus it maintains rigidity and it is being well packed.…”