Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Preparation of Levothyroxine Transdermal Gels and Preliminary Pharmacokinetic Study in Hypothyroidism Rat Model

Author(s): Qingshuang Bai, Jian Tan*, Jinyan Chai, Linna Shen, Ning Li and Cailan Wu

Volume 19, Issue 11, 2022

Published on: 11 April, 2022

Page: [1039 - 1048] Pages: 10

DOI: 10.2174/1570180819666220322151350

Price: $65

conference banner
Abstract

Background: Hypothyroidism is a common disorder due to inadequate thyroid hormone secretion. In patients with hypothyroidism, levothyroxine (LT4) is the treatment of choice, and tablets are the most common dosage form. However, the main limitation of tablet LT4 is malabsorption.

Objective: This study intends to develop a new dosage form of percutaneous drug delivery for levothyroxine. Absorption of levothyroxine sodium through the application of gel formulation was studied using a hypothyroidism rat model.

Methods: A formulation of levothyroxine sodium gel was developed and selected. In vitro transdermal experiments were performed using the vertical Franz diffusion pool method, and gel formulation was used for animal research (hypothyroidism rats model). Total 30 rats were randomly divided into 6 groups, and one was the normal control group. The other 5 groups were prepared as hypothyroidism models. After applying different doses of gel preparation to the rat model, we measured serum total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) using fluorescence determination of luminescence immunoassay.

Results: The optimum formulation of levothyroxine gels comprised 20% polyvinyl alcohol (PVA), 5% glycerol, 2% azone, and 6% oleic acid. The application of levothyroxine sodium gel resulted in quick and smooth action so that the predicted level of the normal control group could be reached within 2 weeks, and it lasted steadily for 8 weeks.

Conclusion: This research study successfully developed and tested an optimal formulation of levothyroxine gel with therapeutic benefit on hypothyroidism in rats.

Keywords: Thyroxine, gels, hypothyroidism, transdermal, absorption, thyroid-stimulating hormone, pharmacokinetic study.

« Previous Next »
Graphical Abstract

[1]
Parretti, H.; Okosieme, O.; Vanderpump, M. Current recommendations in the management of hypothyroidism: Developed from a statement by the British Thyroid Association Executive. Br. J. Gen. Pract., 2016, 66(651), 538-540.
[http://dx.doi.org/10.3399/bjgp16X687493] [PMID: 27688516]
[2]
Castellana, M.; Castellana, C.; Giovanella, L.; Trimboli, P. Prevalence of gastrointestinal disorders having an impact on tablet levothyroxine absorption: Should this formulation still be considered as the first-line therapy? Endocrine, 2020, 67(2), 281-290.
[http://dx.doi.org/10.1007/s12020-019-02185-4] [PMID: 31953721]
[3]
McDermott, M.T. Hypothyroidism. Ann. Intern. Med., 2020, 173(1), ITC1-ITC16.
[http://dx.doi.org/10.7326/AITC202007070] [PMID: 32628881]
[4]
Leung, A.K.C.; Leung, A.A.C. Evaluation and management of the child with hypothyroidism. World J. Pediatr., 2019, 15(2), 124-134.
[http://dx.doi.org/10.1007/s12519-019-00230-w] [PMID: 30734891]
[5]
Hanley, P.; Lord, K.; Bauer, A.J. Thyroid disorders in children and adolescents: A review. JAMA Pediatr., 2016, 170(10), 1008-1019.
[http://dx.doi.org/10.1001/jamapediatrics.2016.0486] [PMID: 27571216]
[6]
Biondi, B.; Cooper, D.S. Thyroid hormone therapy for hypothyroidism. Endocrine, 2019, 66(1), 18-26.
[http://dx.doi.org/10.1007/s12020-019-02023-7] [PMID: 31372822]
[7]
Virili, C.; Trimboli, P.; Centanni, M. Novel thyroxine formulations: A further step toward precision medicine. Endocrine, 2019, 66(1), 87-94.
[http://dx.doi.org/10.1007/s12020-019-02049-x] [PMID: 31617168]
[8]
Skelin, M.; Lucijanić, T.; Amidžić Klarić, D.; Rešić, A.; Bakula, M.; Liberati-Čizmek, A.M.; Gharib, H.; Rahelić, D. Factors affecting gastrointestinal absorption of levothyroxine: A review. Clin. Ther., 2017, 39(2), 378-403.
[http://dx.doi.org/10.1016/j.clinthera.2017.01.005] [PMID: 28153426]
[9]
Virili, C.; Antonelli, A.; Santaguida, M.G.; Benvenga, S.; Centanni, M. Gastrointestinal malabsorption of thyroxine. Endocr. Rev., 2019, 40(1), 118-136.
[http://dx.doi.org/10.1210/er.2018-00168]
[10]
Ceulemans, J.; Ludwig, A. Optimisation of carbomer viscous eye drops: An in vitro experimental design approach using rheological techniques. Eur. J. Pharm. Biopharm., 2002, 54(1), 41-50.
[http://dx.doi.org/10.1016/S0939-6411(02)00036-X]
[11]
Muxika, A.; Etxabide, A.; Uranga, J.; Guerrero, P.; de la Caba, K. Chitosan as a bioactive polymer: Processing, properties and applications. Int. J. Biol. Macromol., 2017, 105(Pt 2), 1358-1368.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.07.087] [PMID: 28735006]
[12]
Schubert, J.; Hahn, J.; Dettbarn, G.; Seidel, A.; Luch, A.; Schulz, T.G. Mainstream smoke of the waterpipe: Does this environmental matrix reveal as significant source of toxic compounds? Toxicol. Lett., 2011, 205(3), 279-284.
[http://dx.doi.org/10.1016/j.toxlet.2011.06.017] [PMID: 21712083]
[13]
Engelke, L.; Winter, G.; Engert, J. Application of water-soluble polyvinyl alcohol-based film patches on laser microporated skin facilitates intradermal macromolecule and nanoparticle delivery. Eur. J. Pharm. Biopharm., 2018, 128, 119-130.
[http://dx.doi.org/10.1016/j.ejpb.2018.04.008] [PMID: 29660407]
[14]
Chen, Z.; Hu, Y.; Li, J.; Zhang, C.; Gao, F.; Ma, X.; Zhang, J.; Fu, C.; Geng, F. A feasible biocompatible hydrogel film embedding Periplaneta americana extract for acute wound healing. Int. J. Pharm., 2019, 571, 118707.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118707] [PMID: 31593807]
[15]
Larrea-Wachtendorff, D.; Di Nobile, G.; Ferrari, G. Effects of processing conditions and glycerol concentration on rheological and texture properties of starch-based hydrogels produced by high pressure processing (HPP). Int. J. Biol. Macromol., 2020, 159, 590-597.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.05.120] [PMID: 32428592]
[16]
Johnson, C.; Olivier, N.B.; Nachreiner, R.; Mullaney, T. Effect of 131I-induced hypothyroidism on indices of reproductive function in adult male dogs. J. Vet. Intern. Med., 1999, 13(2), 104-110.
[http://dx.doi.org/10.1892/0891-6640(1999)013<0104:EOIHOI>2.3.CO;2] [PMID: 10225599]
[17]
Pasteur, I.; Tronko, N.; Drozdovich, I.; Donich, S.; Voitenko, L. Xenotransplantation of cultured newborn pig thyroid tissue for the treatment of post-radioiodine hypothyroidism in rats. Cytotechnology, 2000, 33(1-3), 89-92.
[18]
Reilly, C.P.; Symons, R.G.; Wellby, M.L. A rat model of the 131I-induced changes in thyroid function. J. Endocrinol. Invest., 1986, 9(5), 367-370.
[http://dx.doi.org/10.1007/BF03346944] [PMID: 3794182]
[19]
Torlak, V.; Zemunik, T.; Modun, D.; Capkun, V.; Pesutić-Pisać, V.; Markotić, A.; Pavela-Vrancić, M.; Stanicić, A. 131 I-induced changes in rat thyroid gland function. Braz. J. Med. Biol. Res., 2007, 40(8), 1087-1094.
[http://dx.doi.org/10.1590/S0100-879X2006005000127] [PMID: 17665045]
[20]
Tsai, L.C.; Chen, C.H.; Lin, C.W.; Ho, Y.C.; Mi, F.L. Development of mutlifunctional nanoparticles self-assembled from trimethyl chitosan and fucoidan for enhanced oral delivery of insulin. Int. J. Biol. Macromol., 2019, 126, 141-150.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.12.182] [PMID: 30586591]
[21]
Benvenga, S. L-T4 Therapy in the presence of pharmacological interferents. Front. Endocrinol. (Lausanne), 2020, 11, 607446.
[http://dx.doi.org/10.3389/fendo.2020.607446] [PMID: 33414765]
[22]
Garber, J.R.; Cobin, R.H.; Gharib, H.; Hennessey, J.V.; Klein, I.; Mechanick, J.I.; Pessah-Pollack, R.; Singer, P.A.; Woeber, K.A. American Association Of Clinical Endocrinologists And American Thyroid Association Taskforce On Hypothyroidism In Adults. Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid, 2012, 22(12), 1200-1235.
[http://dx.doi.org/10.1089/thy.2012.0205] [PMID: 22954017]
[23]
Rambharose, S.; Kalhapure, R.S.; Govender, T. Nanoemulgel using a bicephalous heterolipid as a novel approach to enhance transdermal permeation of tenofovir. Colloids Surf. B Biointerfaces, 2017, 154, 221-227.
[http://dx.doi.org/10.1016/j.colsurfb.2017.03.040] [PMID: 28343120]
[24]
Padula, C.; Nicoli, S.; Santi, P. Innovative formulations for the delivery of levothyroxine to the skin. Int. J. Pharm., 2009, 372(1-2), 12-16.
[http://dx.doi.org/10.1016/j.ijpharm.2008.12.028] [PMID: 19162148]
[25]
Kaykhaei, M.A.; Shahraki, M.R.; Mohammadi, M.; Moshtaghian, B.; Zandkarimi, M. The effects of topical application of thyroid hormone (liothyronine, T3) on skin wounds in diabetic wistar rats. Zahedan J. Res. Med. Sci., 2016, 18(4), e6449.
[http://dx.doi.org/10.17795/zjrms-6449]
[26]
Paus, R.; Ramot, Y.; Kirsner, R.S.; Tomic-Canic, M. Topical L-thyroxine: The Cinderella among hormones waiting to dance on the floor of dermatological therapy? Exp. Dermatol., 2020, 29(9), 910-923.
[http://dx.doi.org/10.1111/exd.14156] [PMID: 32682336]
[27]
Kilkenny, C.; Browne, W.J.; Cuthill, I.C.; Emerson, M.; Altman, D.G. Improving bioscience research reporting: The arrive guidelines for reporting animal research. PLoS Biol., 2010, 8(6), e1000412.
[http://dx.doi.org/10.1371/journal.pbio.1000412] [PMID: 20613859]

Rights & Permissions Print Cite
Article Metrics
16
1
© 2024 Bentham Science Publishers | Privacy Policy