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Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear.
Int J Pharm. 2014 Aug 25; 471(1-2):297-302.IJ

Abstract

Intratympanic glucocorticoid therapy aims to reduce the side effects associated with systemic long-time therapy of inner ear diseases or traumata after cochlear implantation. For that purpose, thermoreversible hydrogels being fluid at room temperature but solid at body temperature are known to be appropriate drug delivery systems. In this work, the two key parameters sol-gel transition time and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto-compatible micronized triamcinolone acetonide (TAAc) were evaluated by rheological experiments varying the concentrations of the different compounds. A 20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate formulation. Oscillation-rotation-oscillation studies at two temperature levels were found to be an useful in-vitro test system for the hydrogel which revealed sufficient storage stability at 4 °C, injectability of the sol, solidification within 20s at body temperature and persistent stiffness indicating prolonged adhesion at the round window membrane. According to the in-vitro release studies using the Transwell™ system, absorption of the poor water soluble TAAc is partly due to the low amount of dissolved drug but predominantly due to micellar transport resulting in a cumulative release of 262.6±13.4 μg TAAc within one week followed by a sustained release of 193.1±8.3 μg TAAc within the next three weeks. Thus, the formation of POX 407 micelles is the basis not only for gel formation but also absorptivity of TAAc. All in all, fine tuned rheological experiments and absorption studies emerged as useful tools for preclinical evaluation of intratympanally administered hydrogels.

Authors+Show Affiliations

Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraβe 14, 1090 Vienna, Austria.Department of Otorhinolaryngology, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria.Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraβe 14, 1090 Vienna, Austria.Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraβe 14, 1090 Vienna, Austria.Department of Otorhinolaryngology, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria.Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraβe 14, 1090 Vienna, Austria. Electronic address: franz.gabor@univie.ac.at.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24907595

Citation

Engleder, Elisabeth, et al. "Preclinical Evaluation of Thermoreversible Triamcinolone Acetonide Hydrogels for Drug Delivery to the Inner Ear." International Journal of Pharmaceutics, vol. 471, no. 1-2, 2014, pp. 297-302.
Engleder E, Honeder C, Klobasa J, et al. Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear. Int J Pharm. 2014;471(1-2):297-302.
Engleder, E., Honeder, C., Klobasa, J., Wirth, M., Arnoldner, C., & Gabor, F. (2014). Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear. International Journal of Pharmaceutics, 471(1-2), 297-302. https://doi.org/10.1016/j.ijpharm.2014.05.057
Engleder E, et al. Preclinical Evaluation of Thermoreversible Triamcinolone Acetonide Hydrogels for Drug Delivery to the Inner Ear. Int J Pharm. 2014 Aug 25;471(1-2):297-302. PubMed PMID: 24907595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear. AU - Engleder,Elisabeth, AU - Honeder,Clemens, AU - Klobasa,Julia, AU - Wirth,Michael, AU - Arnoldner,Christoph, AU - Gabor,Franz, Y1 - 2014/06/02/ PY - 2014/03/12/received PY - 2014/05/28/revised PY - 2014/05/29/accepted PY - 2014/6/8/entrez PY - 2014/6/8/pubmed PY - 2015/2/20/medline KW - In-vitro release KW - Intratympanic administration KW - Poloxamer 407 KW - Thermoreversible hydrogel KW - Triamcinolone acetonide SP - 297 EP - 302 JF - International journal of pharmaceutics JO - Int J Pharm VL - 471 IS - 1-2 N2 - Intratympanic glucocorticoid therapy aims to reduce the side effects associated with systemic long-time therapy of inner ear diseases or traumata after cochlear implantation. For that purpose, thermoreversible hydrogels being fluid at room temperature but solid at body temperature are known to be appropriate drug delivery systems. In this work, the two key parameters sol-gel transition time and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto-compatible micronized triamcinolone acetonide (TAAc) were evaluated by rheological experiments varying the concentrations of the different compounds. A 20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate formulation. Oscillation-rotation-oscillation studies at two temperature levels were found to be an useful in-vitro test system for the hydrogel which revealed sufficient storage stability at 4 °C, injectability of the sol, solidification within 20s at body temperature and persistent stiffness indicating prolonged adhesion at the round window membrane. According to the in-vitro release studies using the Transwell™ system, absorption of the poor water soluble TAAc is partly due to the low amount of dissolved drug but predominantly due to micellar transport resulting in a cumulative release of 262.6±13.4 μg TAAc within one week followed by a sustained release of 193.1±8.3 μg TAAc within the next three weeks. Thus, the formation of POX 407 micelles is the basis not only for gel formation but also absorptivity of TAAc. All in all, fine tuned rheological experiments and absorption studies emerged as useful tools for preclinical evaluation of intratympanally administered hydrogels. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/24907595/Preclinical_evaluation_of_thermoreversible_triamcinolone_acetonide_hydrogels_for_drug_delivery_to_the_inner_ear_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(14)00410-4 DB - PRIME DP - Unbound Medicine ER -