Abstract
Three-dimensional-printed customizable drug-loaded implants provide promising opportunities to improve the current therapy options. In this study, we present a modular implant in which shape, dosage, and drug release can be individualized independently of each other to patient characteristics to improve parenteral therapy with triamcinolone acetonide (TA) over three months. This study focused on the examination of release modification via fused deposition modeling and subsequent prediction. The filaments for printing consisted of TA, ethyl cellulose, hypromellose, and triethyl citrate. Two-compartment implants were successfully developed, consisting of a shape-adaptable shell and an embedded drug-loaded network. For the network, different strand widths and pore size combinations were printed and analyzed in long-term dissolution studies to evaluate their impact on the release performance. TA release varied between 8.58 ± 1.38 mg and 21.93 mg ± 1.31 mg over three months depending on the network structure and the resulting specific surface area. Two different approaches were employed to predict the TA release over time. Because of the varying release characteristics, applicability was limited, but successful in several cases. Using a simple Higuchi-based approach, good release predictions could be made for a release time of 90 days from the release data of the initial 15 days (RMSEP ≤ 3.15%), reducing the analytical effort and simplifying quality control. These findings are important to establish customizable implants and to optimize the therapy with TA for specific intra-articular diseases.
Original language | English |
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Article number | 2097 |
Journal | Pharmaceutics |
Volume | 15 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2023 |
Bibliographical note
Publisher Copyright:© 2023 by the authors.
Funding
The authors thank the Drug Delivery Innovation Center (DDIC) for the financial support and for providing the scientific network. Further, the authors would like to thank Dorothee Eikeler for her assistance with filament extrusion and sample preparation during long-term release studies and analysis; Andrea Michel for her support with sampling during the release studies; and Stefan Stich for constructing the implant holder. Raphael Wiedey is acknowledged for his help in the evaluation of the X-ray computed tomography measurements and for providing the method to determine the drug-eluting surface area of implants.
Funders | Funder number |
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Drug Delivery Innovation Center |
Keywords
- 3D printing
- additive manufacturing
- implants
- individualized therapy
- long-term dissolution and prediction
- triamcinolone acetonide