Targeted Development of an Optimised Formulation for 3D-Printing of a Sertraline Hydrochloride-Containing Drug Delivery System with Immediate-Release Characteristics Utilising a Mixture Design.

Abstract

Objectives: Although 3D-printing has been identified as a promising technique for personalised medicine manufacturing, developing complex formulations that are suitable for the process can be challenging. This study evaluates the use of a mixture design for the targeted development of an optimised formulation designed for the 3D-printing of oral dosage forms containing the drug sertraline hydrochloride featuring immediate-release drug dissolution. Methods: The polymers Eudragit E PO, Kollidon 17 PF and hydroxypropyl cellulose were compared in simple screening experiments regarding their extrudability, printability and disintegration. A combination of Eudragit E PO and Kollidon 17 PF proved superior and therefore served as the basis for the mixture design. The resulting blends were processed via hot melt extrusion to produce filaments, which were then measured for bending stress using a 3-point-bending-test, and 3D-printed sample plates were used to determine the crystallinity index of sertraline hydrochloride using X-ray diffraction in a previously identified range with low interference from the other components. The formulation was optimised using statistically based models with the aim of minimising the bending stress to obtain flexible, process-robust filaments and simultaneously minimising the crystallinity index with the intention of improving the solubility of the drug by maximising its amorphous content. Results: The filaments made from the optimised formulation could be reliably printed, and the amorphous state of the active ingredient therein was confirmed. The oral dosage forms produced from these showed immediate release characteristics in an acidic medium. Conclusions: This study demonstrates the advantages of a mixture design for optimising complex formulations in a time- and resource-efficient way and could serve as a basis for other research groups to develop innovative, customisable drug delivery systems more effectively.