Oral drug delivery systems using core-shell structure additive manufacturing technologies: a proof-of-concept study.

Objectives: The aim of this study was to couple fused deposition modelling 3D printing with melt extrusion technology to produce core-shell-structured controlled-release tablets with dual-mechanism drug-release performance in a simulated intestinal fluid medium. Coupling abovementioned technologies for personalized drug delivery can improve access to complex dosage formulations at a reasonable cost. Compared with traditional pharmaceutical manufacturing, this should facilitate the following: (1) the ability to manipulate drug release by adjusting structures, (2) enhanced solubility and bioavailability of poorly water-soluble drugs and (3) on-demand production of more complex structured dosages for personalized treatment.

Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan.

Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pH-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pH-SD formulations by varying the ratio of the drug (TEL, 10-60% /), the hydrophilic polymer (Soluplus, 30-90% ), and pH-modifier (sodium carbonate, 0-10% /).

Continuous Manufacturing of Ketoprofen Delayed Release Pellets Using Melt Extrusion Technology: Application of QbD Design Space, Inline Near Infrared, and Inline Pellet Size Analysis.

Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors propose a novel approach using the hot-melt extrusion technique to prepare delayed release dosage forms via a continuous manufacturing process, a new trend in the pharmaceutical industry. A full factorial design was employed to correlate input variables, including stearic acid (SA) content, drug content, and pellet size with drug release properties of the pellets.

Hot melt extrusion paired fused deposition modeling 3D printing to develop hydroxypropyl cellulose based floating tablets of cinnarizine.

Three-dimensional printing could serve as a platform to fabricate individualized medicines and complex-structured solid dosage forms. Herein, hot melt extrusion was coupled with 3D printing to develop a unique gastro retentive dosage form to personalize treatment of cinnarizine or other narrow absorption window drugs. The mechanical strength of the extruded strands was optimized for printing by combining two polymers, hydroxypropyl cellulose and vinylpyrrolidone vinyl acetate copolymer.

Dual mechanism of microenvironmental pH modulation and foam melt extrusion to enhance performance of HPMCAS based amorphous solid dispersion.

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is an excellent polymeric carrier for melt extrusion amorphous solid dispersion. However, its pH-dependent solubility limits its application, especially for narrow absorption window drugs. The current study proposed a novel dual approach of foam extrusion and microenvironmental pH modulation to overcome this limitation.

Application of FT-NIR Analysis for In-line and Real-Time Monitoring of Pharmaceutical Hot Melt Extrusion: a Technical Note.

Continuous manufacturing, a gaining interest paradigm in the pharmaceutical industry, requires in-process monitoring of critical process parameters to ensure product consistency. This study demonstrated the application of Fourier transform near-infrared (FT-NIR) spectroscopy in conjunction with chemometrics modeling for in-line hot melt extrusion process monitoring. The obtained results suggested that inline FT-NIR analysis, along with a tailored NIR reflector, is a viable process analytical tool to monitor active pharmaceutical ingredient concentration as well as processing parameters.

Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized Drug Delivery Systems.

Inter-individual variability is always an issue when treating patients of different races, genders, ages, pharmacogenetics, and pharmacokinetic characteristics. However, the development of novel dosage forms is limited by the huge investments required for production line modifications and dosages diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative solution for the development of controlled release dosages because it can produce personalized or unique dosage forms and more complex drug-release profiles.

Melt extrusion with poorly soluble drugs - An integrated review.

Over the last few decades, hot melt extrusion (HME) has emerged as a successful technology for a broad spectrum of applications in the pharmaceutical industry. As indicated by multiple publications and patents, HME is mainly used for the enhancement of solubility and bioavailability of poorly soluble drugs. This review is focused on the recent reports on the solubility enhancement via HME and provides an update for the manufacturing/scaling up aspects of melt extrusion.

Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation.

The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses.

Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion.

Unlabelled: In the present study, we aimed to prepare a gastroretentive drug delivery system that would be both highly resistant to gastric emptying via multiple mechanisms and would also potentially induce in situ supersaturation. The bioadhesive floating pellets, loaded with an amorphous solid dispersion, were prepared in a single step of hot-melt extrusion technology. Hydroxypropyl cellulose (Klucel™ MF) and hypromellose (Benecel™ K15M) were used as matrix-forming polymers, and felodipine was used as the model drug.

A novel floating controlled release drug delivery system prepared by hot-melt extrusion.

Floating dosage forms are an important formulation strategy for drugs with a narrow absorption window and low intestinal solubility, and for localized gastric treatment. Novel floating pellets were prepared using the hot-melt extrusion (HME) technology. Uniformly foamed strands were created by liquid injection pumping and screw configuration modification.