Customizable 3D Printed Implants Containing Triamcinolone Acetonide: Development, Analysis, Modification, and Modeling of Drug Release

被引:3
作者
Ponsar, Hanna [1 ,2 ]
Quodbach, Julian [1 ,3 ]
机构
[1] Heinrich Heine Univ, Inst Pharmaceut & Biopharmaceut, Univ Str1, D-40225 Dusseldorf, Germany
[2] INVITE GmbH, Drug Delivery Innovat Ctr DDIC, Chempark Bldg W 32, D-51368 Leverkusen, Germany
[3] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Universiteitsweg 99, NL-3584 CG Utrecht, Netherlands
关键词
3D printing; individualized therapy; implants; triamcinolone acetonide; long-term dissolution and prediction; additive manufacturing; PHARMACOKINETICS; FORMULATION; DEVICES; OSTEOARTHRITIS; TABLETS; INJECTION; SCAFFOLDS; POLYMERS; DELIVERY;
D O I
10.3390/pharmaceutics15082097
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页数:22
相关论文
共 68 条
[1]   Emergence of 3D Printed Dosage Forms: Opportunities and Challenges [J].
Alhnan, Mohamed A. ;
Okwuosa, Tochukwu C. ;
Sadia, Muzna ;
Wan, Ka-Wai ;
Ahmed, Waqar ;
Arafat, Basel .
PHARMACEUTICAL RESEARCH, 2016, 33 (08) :1817-1832
[2]   Modulating antibiotic release from reservoirs in 3D-printed orthopedic devices to treat periprosthetic joint infection [J].
Allen, Brian ;
Moore, Christina ;
Seyler, Thorsten ;
Gall, Ken .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2020, 38 (10) :2239-2249
[3]  
[Anonymous], 2021, VOL 40 A 40 5 ML SUM
[4]   An Intra-Articular, Extended-Release Formulation of Triamcinolone Acetonide Prolongs and Amplifies Analgesic Effect in Patients with Osteoarthritis of the Knee [J].
Bodick, Neil ;
Lufkin, Joelle ;
Willwerth, Christina ;
Kumar, Anjali ;
Bolognese, James ;
Schoonmaker, Chris ;
Ballal, Rahul ;
Hunter, David ;
Clayman, Michael .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2015, 97A (11) :877-888
[5]  
Burgess Diane J, 2004, AAPS PharmSci, V6, pE11
[6]  
Center for Drug Evaluation and Research (CDER), 1994, REV GUID
[7]   Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study [J].
Conaghan, Philip G. ;
Hunter, David J. ;
Cohen, Stanley B. ;
Kraus, Virginia B. ;
Berenbaum, Francis ;
Lieberman, Jay R. ;
Jones, Deryk G. ;
Spitzer, Andrew, I ;
Jevsevar, David S. ;
Katz, Nathaniel P. ;
Burgess, Diane J. ;
Lufkin, Joelle ;
Johnson, James R. ;
Bodick, Neil .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2018, 100 (08) :666-677
[8]   Additive manufacturing of scaffolds with dexamethasone controlled release for enhanced bone regeneration [J].
Costa, Pedro F. ;
Puga, Ana M. ;
Diaz-Gomez, Luis ;
Concheiro, Angel ;
Busch, Dirk H. ;
Alvarez-Lorenzo, Carmen .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 496 (02) :541-550
[9]   PHARMACOKINETICS OF TRIAMCINOLONE ACETONIDE AFTER INTRAVENOUS, ORAL, AND INHALED ADMINISTRATION [J].
DERENDORF, H ;
HOCHHAUS, G ;
ROHATAGI, S ;
MOLLMANN, H ;
BARTH, J ;
SOURGENS, H ;
ERDMANN, M .
JOURNAL OF CLINICAL PHARMACOLOGY, 1995, 35 (03) :302-305
[10]   PHARMACOKINETICS AND PHARMACODYNAMICS OF GLUCOCORTICOID SUSPENSIONS AFTER INTRAARTICULAR ADMINISTRATION [J].
DERENDORF, H ;
MOLLMANN, H ;
GRUNER, A ;
HAACK, D ;
GYSELBY, G .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 39 (03) :313-317