Fabrication of a shell-core fixed-dose combination tablet using fused deposition modeling 3D printing

Abdullah Alzahrani; Sagar Narala; Ahmed Adel Ali Youssef; Dinesh Nyavanandi; Suresh Bandari; Preethi Mandati; Ahmed Almotairy; Mashan Almutairi; Michael Repka

doi:10.1016/j.ejpb.2022.07.003

Fabrication of a shell-core fixed-dose combination tablet using fused deposition modeling 3D printing

Eur J Pharm Biopharm. 2022 Aug:177:211-223. doi: 10.1016/j.ejpb.2022.07.003. Epub 2022 Jul 11.

Authors

Abdullah Alzahrani¹, Sagar Narala², Ahmed Adel Ali Youssef³, Dinesh Nyavanandi², Suresh Bandari², Preethi Mandati², Ahmed Almotairy⁴, Mashan Almutairi⁵, Michael Repka⁶

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah 22253, Saudi Arabia.
² Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
³ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
⁴ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, 30001, Saudi Arabia.
⁵ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia.
⁶ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA. Electronic address: marepka@olemiss.edu.

PMID: 35835328
DOI: 10.1016/j.ejpb.2022.07.003

Abstract

Fixed-dose combinations (FDCs) achieve optimal goals for treatment with minimal side effects, decreased administration of large number of tablets, thus, greater convenience, and improved patient compliance. However, conventional FDCs do not have a guaranteed place in the future of patient-centered drug development because of the difficulty in achieving dose titration of each drug for individualized specific health needs and desired therapeutic outcomes. In the current study, FDCs of two antihypertensive drugs were fabricated with two distinct compartments using fused deposition modeling three-dimensional printing (FDM-3DP). Atorvastatin calcium and Amlodipine besylate loaded filaments were prepared by hot-melt extrusion. Shell-core FDC tablets were designed to have different infills for individualized dosing. Differential scanning calorimetry and powder X-ray diffraction revealed that both drugs were transformed into amorphous forms within the polymeric carriers. The fabricated tablets met the United States Pharmacopeia acceptance criteria for friability, content uniformity, and dissolution testing. The fabricated tablets were stable at room temperature with respect to drug content and thermal behavior over six months. This dynamic dosage form provides flexibility in dose titration and maintains the advantages of FDCs, thus achieving optimal therapeutic outcomes in different healthcare facilities.

Keywords: 3D printing; Fixed-dose combination; Fused deposition modeling; Hot-melt extrusion; Personalized therapy; Shell-core design; Solid dispersion.

MeSH terms

Calorimetry, Differential Scanning
Drug Liberation
Humans
Powders
Printing, Three-Dimensional*
Tablets / chemistry
Technology, Pharmaceutical* / methods

Substances

Powders
Tablets