Influence of Dissolution Vessel Geometry and Dissolution Medium on In Vitro Dissolution Behaviour of Triamterene-Coated Model Stents in Different Test Setups
- 37 Downloads
The aim of this study was to investigate if the geometry of the dissolution vessel, the dissolution medium volume and composition might contribute to the variation in drug release from drug-eluting stents (DES) in different test setups, which has been observed in previous in vitro studies. Therefore, DES containing triamterene as model substance were produced via fluidised-bed technology. Dissolution testing was carried out using different incubation setups, the reciprocating holder (USP Apparatus 7) and two flow-through methods, a method similar to the USP Apparatus 4 (FTC) and the vessel-simulating flow-through cell (vFTC) equipped with a hydrogel as a second compartment simulating the blood vessel wall. The results indicate that dissolution vessel geometry and medium volume had no influence on the release behaviour and only the flow-through cell methods yielded a lower dissolution rate than the incubation setups (80.6 ± 2.0% released in the FTC after 14 days compared to > 90% for all incubation setups). The composition of the hydrogel used in the vFTC also affected the dissolution rate (53.9 ± 4.5% within 14 days with a hydrogel based on phosphate-buffered saline compared to 78.2 ± 1.2% obtained with a hydrogel based on water) possibly due to different solubility of triamterene in the release media as well as interactions between the coating polymer and the release medium. Hence, the introduction of a hydrogel as a second compartment might lead to a more biorelevant test setup.
KEY WORDSdrug-eluting stent in vitro dissolution testing vessel-simulating flow-through cell fluidised-bed technology release medium
The authors thank Agilent Technologies, Inc., USA, and Prof. Sandra Klein for the supply of the 400-DS reciprocating holder apparatus and Katharina Tietz for assistance with the experiments. Furthermore, the authors thank Biotronik SE & Co. KG and Evonik Nutrition and Care GmbH for providing BMS and Eudragit® RS 30 D. The expert technical assistance of Thomas Brand, Sabine Ristow, Johann Schopplich and David Heldner is gratefully acknowledged. The authors also thank the staff of the technical workshop of the Faculty of Mathematics and Natural Sciences, University of Greifswald for the construction of the flow-through cells.
This work was funded by the Federal Ministry of Education and Research (BMBF) within RESPONSE.
- 18.Sternberg K, Kramer S, Nischan C, Grabow N, Langer T, Hennighausen G, et al. In vitro study of drug-eluting stent coatings based on poly(L-lactide) incorporating cyclosporine A—drug release, polymer degradation and mechanical integrity. J Mater Sci Mater Med. 2007;18(7):1423–32.CrossRefGoogle Scholar
- 25.Council of Europe (ed.). European pharmacopoeia 9th edition, 4.1.3 buffer solutions. 2019.Google Scholar
- 26.Wentzlaff M, Seidlitz A, Senz V, Grabow N, Harder C, Sternberg K, et al. Investigating the applicability of fluidized-bed technology for high-throughput coating of stents. Biomed Tech. 2013;58(1):24–5.Google Scholar
- 30.United States Pharmacopeial Convention Inc. Council of Experts (ed.). United States Pharmacopeia and National Formulary USP 41-NF 36 <711> Dissolution.Google Scholar
- 45.Serajuddin ATM, Mufson D. pH-solubility profiles of organic bases and their hydrochloride salts. Vol. 2, Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1985. p. 65–8.Google Scholar