ORCID

https://orcid.org/0009-0003-5855-2297

Date of Award

2025

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences (Ph.D.)

Department

Pharmaceutical Sciences

First Advisor

Abu T Serajuddin

Second Advisor

Nitesh K Kunda,

Third Advisor

Ketan D Patel

Abstract

In recent years, there has been much interest in three-dimensional (3D) printing for the development of personalized and on-demand medications for better therapy. In 3D-printing, materials are deposited layer by layer to form tablets and pellets. Among various 3D-printing technologies, the fused deposition modeling (FDM) 3D printing, where melt-extruded filaments of drug-polymer mixtures are used for 3D printing, is most promising. However, the FDM 3D-printing often produces slow-release tablets that are not suitable for rapid drug action in the body. The present investigation was undertaken to demonstrate how rapidly dissolving 3D-printed tablets of poorly water-soluble acidic drugs could be developed using amorphous solid dispersions (ASD) prepared by applying the acid-base supersolubilization (ABS) principle. Two model drugs, flurbiprofen and telmisartan, were used to demonstrate the application ABS principle to increase dissolution rates of acidic drugs, and flurbiprofen was then used for 3D-printing. Flurbiprofen is a weakly acidic drug (pKa 4.2) with aqueous solubility of 0.005-0.010 mg/mL (5-10 µg/mL). By adjusting pH in aqueous media by using bases like meglumine, lysine, tromethamine and sodium hydroxide, it has been demonstrated that flurbiprofen exhibited acid-base supersolubilization (ABS) with the increase in solubility to >347 mg/g in presence of meglumine, while crystallization of salts occurred for other bases. Dried flurbiprofen-meglumine solutions produced ASDs with rapid drug dissolution rates. Rapidly dissolving ASDs were also formed when mixtures of flurbiprofen with meglumine and Kollidon® VA 64 were melt-extruded. Filaments produced by such ternary mixtures were, however, brittle and not printable. The printability of tablets was improved by the addition of Affinisol™ E15 or Aeroperl® 300, and the tablets still had rapid dissolution rates. The solubility of the second acidic drug, telmisartan, could be increased from < 0.0001 mg/mL (0.1µg/mL) to >300 mg/g in presence of meglumine by applying the ABS principle. Despite very high melting point of telmisartan (261-263ºC), ASDs were formed when telmisartan-meglumine-Kollidon® VA64 mixtures were melt-extruded into filaments at 130°C. Dissolution testing of crushed filaments with meglumine showed complete drug release within 10 minutes. The application of ABS principle in the present investigation solved a major challenge in the development of FDM 3D printed tablets.

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