Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Abstract

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid-State, and Quality of 3D Printed Dosage Forms

“…Different NFD concentrations were prepared (20,40,80, 160 µg/mL) using methanol as a solvent, and their respective absorbance spectrum was collected using a UV-Visible spectrophotometer (Agilent Cary 8454 UV-Vis Diode Array System, Agilent Technologies, Santa Clara, CA). Considering the concentration-based limitations of liquid state quantitative analysis as per Lambert-beer's law, qualitative investigation of NFD was conducted using a UV-vis reflectance probe with a 316L Stainless Steel/Nickel alloy tip and sapphire window, which was developed to analyze the absorbance of solid samples.…”

“…Previous studies depicting the use of SLS in dosage form development have revolved around immediate release dosage forms 17 , orally disintegrating tablets 18 , modified released dosage forms, and multi-drug releasing systems 19 . Apart from modifying the performance using formulation approaches, researchers have also demonstrated a change in the performance of the dosage forms by merely adjusting the processing parameter 20 . Moreover, this heat-based fusion technique has also been used for the one-step manufacturing of amorphous solid dispersions (ASD) of thermolabile species 14 .…”

Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate

“…26 Multiple 3-DP techniques have found application in pharmaceutical processing especially fused-deposition modeling, wherein ASDs have been processed into 3-D printed tablets. 27 Although FDM has been successful in developing patient-specific, controlled release formulations for ASDs, and finds utility due to its capability of printing complex structures, it is dependent on techniques such as HME to create these ASDs before printing them. 28 The capability for SLS-3DP to provide patient-tailored medications and fixed-dose combinations has been established but, applying the SLS-3DP process to improve the solubility of poorly water-soluble drugs by forming an amorphous solid dispersion has not been investigated.…”

3D Printing: Advancement in Biogenerative Engineering to Combat Shortage of Organs and Bioapplicable Materials

“…This enhancement of drug solubility using FDM filaments which are created with ASD formulations is done by locking the active drug compounds into a formulated filament. This reduces the potential misuse of drug treatment during the panic of an ongoing crisis [164,166]. Furthermore, 3D printing has already been used to produce respirator valves for the ventilators in Italy [167].…”