On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing

Abstract

A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs.

Current formulation approaches in design and development of solid oral dosage forms through three-dimensional printing

“…3). Multi-material 3D printing of tablets includes several examples, like multilayer polypills and composite tablets, where different layers may consist of different polymers to control dissolution behaviour, or liquid-filled capsules [7][8][9]; a further relevant example of design-driven drug release mechanisms is subsequently shown in Fig. 4.…”

An Overview of 3D Printing Technologies for Soft Materials and Potential Opportunities for Lipid-based Drug Delivery Systems

“…The high processing temperature during extrusion can degrade active pharmaceutical compounds and/or excipients. However, the issue can be avoided by using novel polymers that print at lower temperatures (55,56) or including the drug inside the formulation without incorporation into the filament (102)(103)(104). A way to avoid the incorporation of the drug in the filament is to print the shell of the tablet using FDM and to include the drug in the middle in liquid, powder or semi-solid form ( Figure 2).…”

“…A dual head 3D printer was modified by replacing the right-hand nozzle with a syringe dispenser. The FDM nozzle head was loaded with HME processed drug-free filament whilst drug solution or suspension is incorporated inside the formulations using a syringe dispenser.Figure adaptedwith permission from reference(102).…”

Embedded 3D Printing of Novel Bespoke Soft Dosage Form Concept for Pediatrics

“…Several reports have showed the potential of 3D printing in controlling dosage [13,14], drug combination [15][16][17], and proposed modification of pediatric-friendly shapes [18][19][20][21]. However, there are limited examples of using 3D printing for fabrication of patient-specific chewable oral dosage forms.…”