Extruded filaments derived 3D printed medicated skin patch to mitigate destructive pulmonary tuberculosis: design to delivery

ABSTRACT

Background: Quercetin in combination with polyvinylpyrrolidone (PVP) was found to limit the spreading of necrosis to unaffected tissues in tuberculosis-infected mice. Therefore, we hypothesized that 3D printed medicated skin patch incorporated with a quercetin-PVP combination would provide an appropriate therapeutic drug concentration with desired sustained release profile.

Research design and methods: We fabricated quercetin-PVP 40 extruded-filaments by hot-melt extrusion (HME) technique along with Eudragit® RSPO and tri-ethyl citrate and further printed it to make medicated skin patches using fused deposition modeling (FDM) based 3D Printing technology. Various characterizations were performed to optimize the 3D-printed patch formulation.

Results: Patch formulation has been optimized for several characterization parameters and was further assessed using SEM, DSC, and XRD studies to confirm the conversion of crystalline quercetin into an amorphous form. Finally, the pharmacokinetic profile of an optimized patch was studied in rats showing prolonged T_max, lowered C_max, and reduced fluctuations in plasma concentrations till 18 days with single skin application of 3D-printed medicated patch.

Conclusion: Overall data confirmed the feasibility of developing 3D printed medicated skin patches to provide plasma levels for continued 18 days in rats after a single application.

KEYWORDS:

• Hot-melt Extrusion (HME)
• fused deposition modeling (FDM)
• 3D Printing
• filaments
• medicated skin patch
• quercetin-PVP

Acknowledgments

The corresponding author sincerely acknowledges the financial support of S&T Division, ASTE Councilby Department of Science & Technology (DST), Government of Assam under ITGA-2019 schemevide F.No ASTEC/S&T/1614/8/2018-19/1151 for the project titled “Medicated Skin Patch to mitigate destructive pulmonary tuberculosis in six districts of Assam”.

XRD and FESEM studies were supported by the Ministry of Electronics and Information Technology, Government of India [Grant 5(9)/2012- NANO, Vol. IV] through the Centre for Nanotechnology (CNT), IIT Guwahati, Assam, which is greatly acknowledged.

Finally, we sincerely thank Dr. Pavan Kumar Samudrala, Assistant Professor, and Mr. Kamlesh Choudhary, Department of Pharmacology & Toxicology, NIPER Guwahati for rendering assistance during the pharmacokinetic study.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This work is funded through Science and Technology (S&T) Division, Assam Science Technology and Environment (ASTE) Council by Department of Science & Technology (DST), Government of Assam under the scheme Innovation, Technology Generation, and Awareness (ITGA)-2019 scheme vide sanction letter no. ASTEC/S&T/1614/8/2018-19/1151 for the project titled ‘Medicated skin patch to mitigate destructive pulmonary tuberculosis in six districts of Assam’.