Polymer Selection for Hot-Melt Extrusion Coupled to Fused Deposition Modelling in Pharmaceutics

Abstract

Three-dimensional (3D) printing offers the greatest potential to revolutionize the future of pharmaceutical manufacturing by overcoming challenges of conventional pharmaceutical operations and focusing design and production of dosage forms on the patient’s needs. Of the many technologies available, fusion deposition modelling (FDM) is considered of the lowest cost and higher reproducibility and accessibility, offering clear advantages in drug delivery. FDM requires in-house production of filaments of drug-containing thermoplastic polymers by hot-melt extrusion (HME), and the prospect of connecting the two technologies has been under investigation. The ability to integrate HME and FDM and predict and tailor the filaments’ properties will extend the range of printable polymers/formulations. Hence, this work revises the properties of the most common pharmaceutical-grade polymers used and their effect on extrudability, printability, and printing outcome, providing suitable processing windows for different raw materials. As a result, formulation selection will be more straightforward (considering the characteristics of drug and desired dosage form or release profile) and the processes setup will be more expedite (avoiding or mitigating typical processing issues), thus guaranteeing the success of both HME and FDM. Relevant techniques used to characterize filaments and 3D-printed dosage forms as an essential component for the evaluation of the quality output are also presented.

Thermal Stability of Amorphous Solid Dispersions

“…Recent advances in HME and SD expedited commercial and industrial application of amorphous solid dispersion concepts for poorly soluble drugs [ 67 , 70 , 103 , 104 ]. Examples of commercially available drugs include HME (lumacaftor/HPMCAS/SLS, posaconazole/HPMCAS, griseofluvin/PEG, ritonavir/PVP/PA, lopinavir/PVP/VA), and SD (telaprevir/HPMCAS, etravirine/HPMC, itroconazol/HPMC, tacrolimus/HPMC, rosuvastatin/HPMC) [ 105 , 106 ]. The overviewed and quantified information on molecular mobility, crystallization behavior and component miscibility are of great importance for successful formulation of amorphous solid dispersions by HME and SD.…”

Additive Manufacturing of Polymer Materials: Progress, Promise and Challenges

“…Besides traditional plastic components, this process has been adopted for a wide range of industries for innovative product development including soft magnets [ 62 ], drug delivery systems in the pharmaceutical field including personalized medicines [ 63 , 64 , 65 , 66 ], in the forensic comparative analysis [ 67 ], in complete electrochemical sensing devices fabrication [ 68 ], in 3D printed microfluidics [ 69 ] and to design and manufacturing of complex porous scaffolds for biomedical, and tissue engineering applications [ 70 ]. Moreover, it also fits well in the framework of primary and secondary recycling.…”

Influence of the Infill Geometry of 3D-Printed Tablets on Drug Dissolution

“…This technique requires prior drug incorporation in the matrix (e.g., thermoplastic polymers) and the production of filaments (FIL) through hot-melt extrusion (HME). FIL are in turn fed into the 3D-printer, molten and deposited layer-by-layer to build the dosage form [1]. The extrudability and printability of FIL depend on the raw materials (adjusted qualitatively and quantitatively, as required) and the processing conditions [1].…”

“…FIL are in turn fed into the 3D-printer, molten and deposited layer-by-layer to build the dosage form [1]. The extrudability and printability of FIL depend on the raw materials (adjusted qualitatively and quantitatively, as required) and the processing conditions [1]. Since both HME and FDM rely on the fusion of the matrix, the heat stability of the drug is paramount.…”