An Insight into the Impact of Thermal Process on Dissolution Profile and Physical Characteristics of Theophylline Tablets Made through 3D Printing Compared to Conventional Methods

Abstract

The dissolution profile is of great importance in drug delivery and is affected by the manufacturing method. Thus, it is important to study the influence of the thermal process on drug release in emerging technologies such as 3D printing-fused deposition modeling (FDM). For this purpose, the characteristics of 3D printed tablets were compared to those of tablets prepared by other thermal methods such as hot-melt extrusion (HME) and non-thermal methods such as physical mixture (PM). Theophylline was used as a drug model and blends of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were used as a matrix former. The solid state of the drug in all formulations was investigated by differential scanning calorimetry, X-ray powder diffraction, and Fourier-transformed infrared spectroscopy. All studied tablets had the same weight and surface area/volume (SA/V). Dissolution data showed that, for some formulations, printed tablets interestingly had a faster release profile despite having the highest hardness values (>550 N) compared to HME and PM tablets. Porosity investigations showed that 100% infill printed tablets had the highest porosity (~20%) compared to HME (<10%) and PM tablets (≤11%). True density records were the lowest in printed tablets (~1.22 g/m3) compared to tablets made from both HME and PM methods (~1.26 g/m3), reflecting the possible increase in polymer specific volume while printing. This increase in the volume of polymer network may accelerate water and drug diffusion from/within the matrix. Thus, it is a misconception that the 3D printing process will always retard drug release based on increased tablet hardness. Hardness, porosity, density, solid-state of the drug, SA/V, weight, and formulation components are all factors contributing to the release profile where the total balance can either slow down or accelerate the release profile.

Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms

“…Furthermore, evaluation of DSC at temperatures above 250 °C showed endothermic events, due to beginning of the thermal degradation for the polymers, as already described. Detection of distinct T g for HEC and HPC was not possible, as reported in other studies [ 48 , 49 ]. However, the decrease in extrusion temperatures when HPC was added to the HEC grades could indicate a decrease in T g .…”

Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures

“…EC was plasticised with 5% DBS, which was left overnight for better sorption of the plasticizer into the polymer matrix. HPC, EC and theophylline were selected because they are thermally stable materials under the used conditions [16]. The formulations were converted to tablets by three different manufacturing methods, which are described in Section 2.3 below.…”

“…With the current increasing interest in 3D-printing technology for tablet manufacture, it is crucial to investigate the mechanisms involved in the process that impact the dissolution profile of such tablets. Dissolution profile changes after 3D printing may be associated with changes in the porosity, density and hardness, depending on the formulation and printing conditions [16,17]. Thus, a discriminatory dissolution testing method is needed to provide a better understanding of how the printing method can change the release behaviour of a given formulation, which will consequently influence the bioavailability.…”

“…This work investigates how the printing method can change the release profile under harsh dissolution conditions such as high agitation rates and high ionic strengths. In the authors' previous work [16], dissolution studies were carried out in USP 2, while in this paper, more harsh dissolution conditions were applied using a USP 3 apparatus to predict the in vivo behaviour of printed tablets. To the best of the authors' knowledge, this is the first time a USP 3 apparatus has been utilized for a comparison study of the dissolution profile of printed tablets with tablets prepared by conventional manufacturing methods, either from physical mixtures of the formulation powders (PM) or from filaments obtained through the hot-melt extrusion of the same formulation (HME).…”

A Refined Hot Melt Printing Technique with Real-Time CT Imaging Capability

“…There is an enormous interest in pharmaceutical fabrication via 3D printing due to the ability to develop personalized medicine with tailored therapeutic properties [ 14 , 15 , 16 , 17 ]. The advantage of a personalized drug delivery system (DDS) over conventional methods of tablet consumption is that it does not operate on a one size fits all approach.…”