Skip to main content
SpringerLink
Log in

Formulation and Evaluation of Eudragit® RL Polymeric Double Layer Films for Prolonged-Release Transdermal Delivery of Tamsulosin Hydrochloride

AAPS PharmSciTech Aims and scope Submit manuscript

Cite this article

Abstract

Transdermal drug delivery systems (TDDSs) were developed for prolonged tamsulosin (TMS) delivery. Double layer (DL) TDDSs were prepared using Eudragit® RL by conventional film-forming. Ethylene-vinyl acetate was used as the backing layer, triethylcitrate as plasticizer, and Capmul® PG-8-70 NF and Captex 170 EP as penetration enhancers (PEs). An increase in either drug or PE concentration caused a significant increase in drug permeation flux. Modulation of drug permeation across Strat-M® membrane was examined using a single layer (SL) having the same thickness and drug content as the DLs, while the DLs were formulated to have variable drug spatial distribution across each layer (DL 4:6 and DL 6:4). SL/TDDS showed significantly higher daily drug permeation than DL/TDDSs for the first 4 days which could be related to the presence of high TMS concentration located on the upper surface of SL/TDDS as a result of solute migration of TMS during the drying process. However, this increase was followed by a progressive linear decrease after 5 days. Deflection points that were characterized by lower drug flux had been shown by SL/TDDS at more than one-point times. In contrast, DL 4:6 and DL 6:4 TDDSs demonstrated an ability to sustain TMS delivery for up to 2 weeks.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Dunn CJ, Matheson A, Faulds DM. Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms. Drugs Aging. 2002;19(2):135–61. https://doi.org/10.2165/00002512-200219020-00004.

    Article  CAS  PubMed  Google Scholar 

  2. Chughtai B, Forde JC, Thomas DD, Laor L, Hossack T, Woo HH, et al. Benign prostatic hyperplasia. Nat Rev Dis Primers. 2016;2(1):16031. https://doi.org/10.1038/nrdp.2016.31.

    Article  PubMed  Google Scholar 

  3. Unnikrishnan R, Almassi N, Fareed K. Benign prostatic hyperplasia: evaluation and medical management in primary care. Clev Clin J Med. 2017;84(1):53–64. https://doi.org/10.3949/ccjm.84a.16008.

    Article  Google Scholar 

  4. Abrams P, Speakman M, Stott M, Arkell D, Pocock R. A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist, in patients with benign prostatic obstruction (symptoms benign prostatic hyperplasia). Br J Urol. 1997;80(4):587–96. https://doi.org/10.1046/j.1464-410x.1997.00380.x.

    Article  CAS  PubMed  Google Scholar 

  5. Kawahara K, Nakao K, Yamaki H. Inventors. Tamsulosin-containing transdermal patch. U.S. Patent US 2009/0155343 A1, 2009.

  6. Chapple CR. The oral controlled absorption system (OCAS®): the evolution of tamsulosin for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). Eur Urol Suppl. 2005;4(7):20–2. https://doi.org/10.1016/j.eursup.2005.07.006.

    Article  CAS  Google Scholar 

  7. Emberton M, Cornel EB, Bassi PF, Fourcade RO, Gómez JMF, Castro R. Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management. Int J Clin Pract. 2008;62(7):1076–86. https://doi.org/10.1111/j.1742-1241.2008.01785.x.

    Article  CAS  PubMed  Google Scholar 

  8. Chaplin S, Kirby R. Alpha-blockers in the treatment of benign prostatic hypertrophy. Prescriber. 2013;24(4):13–5. https://doi.org/10.1002/psb.1015.

    Article  Google Scholar 

  9. Prausnitz M, Langer R. Transdermal drug delivery Nat biotechnol. 2008;26:1261–8. https://doi.org/10.1038/nbt.1504.

    Article  CAS  PubMed  Google Scholar 

  10. Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: a review. Biomater Res. 2021;25:24. https://doi.org/10.1186/s40824-021-00226-6.

    Article  PubMed  PubMed Central  Google Scholar 

  11. PubChem Compound Summary for CID 129211, Tamsulosin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/129211. Accessed 31 Jan 2022.

  12. Franco-Salinas G, de la Rosette JJ, Michel MC. Pharmacokinetics and pharmacodynamics of tamsulosin in its modified-release and oral controlled absorption system formulations. Clin Pharmacokinet. 2010;49(3):177–88. https://doi.org/10.2165/11317580-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  13. Ma X, Audett J, Soni PL, Singh N, Bailey SE. Inventors. Transdermal drug delivery system for the administration of tamsulosin, and related compositions and methods of use. U.S. Patent US 5,843,472 A, 1998.

  14. Wang Z, Itoh Y, Hosaka Y, Kobayashi I, Nakano Y, Maeda I, et al. Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer. J Biosci Bioeng. 2003;95(5):541–3. https://doi.org/10.1016/S1389-1723(03)80059-2.

    Article  CAS  PubMed  Google Scholar 

  15. Singh P, Lee ES, Jain AK. Inventors. Transdermal administration of tamsulosin. U.S. Patent US 9610253 B2, 4 April 2017.

  16. Almehmady AM, Elsisi AM. Development, optimization, and evaluation of tamsulosin nanotransfersomes to enhance its permeation and bioavailability. JDDST. 2020;57:101667. https://doi.org/10.1016/j.jddst.2020.101667.

    Article  CAS  Google Scholar 

  17. Ciríaco SL, Carvalho IPS, Alves Terceiro Neto J, de Sousa Lima Neto J, DHB d O, Cunha APGP, et al. Development of microemulsion of tamsulosin and dutasteride for benign prostatic hyperplasia therapy. Colloids Surf B Biointerfaces. 2020;185:110573. https://doi.org/10.1016/j.colsurfb.2019.110573.

    Article  CAS  PubMed  Google Scholar 

  18. Assaf SM, Sallam AS, Ghanem AM. Design and evaluation of transdermal delivery system containing tamsulosin hydrochloride. JDDST. 2019;51:524–34. https://doi.org/10.1016/j.jddst.2019.03.023.

    Article  CAS  Google Scholar 

  19. Gao Y, Liang J, Liu J, Xiao Y. Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol. Int J Pharm. 2009;377(1–2):128–34. https://doi.org/10.1016/j.ijpharm.2009.05.017.

    Article  CAS  PubMed  Google Scholar 

  20. Davis DA, Martins PP, Zamloot MS, Kucera SA, Williams RO 3rd, Smyth HDC, Warnken ZN. Complex drug delivery systems: controlling transdermal permeation rates with multiple active pharmaceutical ingredients. AAPS PharmSciTech. 2020;21(5):165. https://doi.org/10.1208/s12249-020-01682-4.

    Article  CAS  PubMed  Google Scholar 

  21. Abitec announces two lipid enhancers for drug delivery. Available online: https://www.abiteccorp.com/en/news-and-events/news/abitec-announces-two-lipid-enhancers-for-drug-delivery/. Accessed 31 Jan 2022.

  22. Gwak HS, Chun IK. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin. Int J Pharm. 2002;236(1–2):57–64. https://doi.org/10.1016/s0378-5173(02)00009-1.

    Article  CAS  PubMed  Google Scholar 

  23. Cho YA, Gwak HS. Transdermal delivery of ketorolac tromethamine: effects of vehicles and penetration enhancers. Drug Dev Ind Pharm. 2004;30(6):557–64. https://doi.org/10.1081/ddc-120037486.

    Article  CAS  PubMed  Google Scholar 

  24. Theobald F, Rubenacher R. Inventors. LTS Lohmann Therapie Systeme GmbH and Co KG, Assignee. Transmittal therapeutic systems containing steroid hormones and propylene glycol monocaprylate. U.S. Patent US 20050118244 A1, 2 June 2005.

  25. Cho CW, Kim DB, Cho HW, Shin SC. Enhanced controlled transdermal delivery of ambroxol from the EVA matrix. Indian J Pharm Sci. 2012;74(2):127–32. https://doi.org/10.4103/0250-474X.103844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Haque T, Talukder MMU. Chemical enhancer: a simplistic way to modulate barrier function of the stratum corneum. Adv Pharm Bull. 2018;8(2):169–79. https://doi.org/10.15171/apb.2018.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263–71. https://doi.org/10.1208/s12248-010-9185-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Experience the unmatched predictability of Strat-M™ membrane. Available online: https://dicsa.es/assets/downloads/2018-13609_Strat-M_membrane_product_brochure_MRK_Web_DP.pdf. Accessed 31 Jan 2022.

  29. Pan TL, Wang PW, Aljuffali IA, Hung YY, Lin CF, Fang JY. Dermal toxicity elicited by phthalates: evaluation of skin absorption, immunohistology, and functional proteomics. Food Chem Toxicol. 2014;65:105–14. https://doi.org/10.1016/j.fct.2013.12.033.

    Article  CAS  PubMed  Google Scholar 

  30. Flaten GE, Palac Z, Engesland A, Filipović-Grčić J, Vanić Ž, Škalko-Basnet N. In vitro skin models as a tool in optimization of drug formulation. Eur J Pharm Sci. 2015;75:10–24. https://doi.org/10.1016/j.ejps.2015.02.018.

    Article  CAS  PubMed  Google Scholar 

  31. Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit® E PO solid dispersion: a simple and potent method to solve the problems of curcumin. Eur J Pharm Biopharm. 2015;94:322–32. https://doi.org/10.1016/j.ejpb.2015.06.002.

    Article  CAS  PubMed  Google Scholar 

  32. Uchida T, Kadhum WR, Kanai S, Todo H, Oshizaka T, Sugibayashi K. Prediction of skin permeation by chemical compounds using the artificial membrane, Strat-M™. Eur J Pharm Sci. 2015;67:113–8. https://doi.org/10.1016/j.ejps.2014.11.002.

    Article  CAS  PubMed  Google Scholar 

  33. Beriro DJ, Cave MR, Wragg J, Thomas R, Wills G, Evans F. A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil. J Hazard Mater. 2016;305:240–59. https://doi.org/10.1016/j.jhazmat.2015.11.010.

    Article  CAS  PubMed  Google Scholar 

  34. Simon A, Amaro MI, Healy AM, Cabral LM, de Sousa VP. Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation. Int J Pharm. 2016;512(1):234–41. https://doi.org/10.1016/j.ijpharm.2016.08.052.

    Article  CAS  PubMed  Google Scholar 

  35. Haq A, Goodyear B, Ameen D, Joshi V, Michniak-Kohn B. Strat-M® synthetic membrane: permeability comparison to human cadaver skin. Int J Pharm. 2018;547(1–2):432–7. https://doi.org/10.1016/j.ijpharm.2018.06.012.

    Article  CAS  PubMed  Google Scholar 

  36. Salamanca CH, Barrera-Ocampo A, Lasso JC, Camacho N, Yarce CJ. Franz diffusion cell approach for pre-formulation characterisation of ketoprofen semi-solid dosage forms. Pharmaceutics. 2018;10(3):148. https://doi.org/10.3390/pharmaceutics10030148.

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the Target Chemicals, Jordan, for donating Eudragit® RL and Al Taqaddom Pharmaceuticals Industries, Jordan, for providing tamsulosin hydrochloride.

Funding

This research was funded by the Jordan University of Science and Technology grant number 20200116.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P. O. Box 3030, Irbid, 22110, Jordan

    Shereen M. Assaf, Aya M. Ghanem & Shayma’a A. Alhaj

  2. Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman, 11942, Jordan

    Enam A. Khalil

  3. Al Taqaddom Pharmaceuticals Industries, P.O. Box 960761, Amman, 11196, Jordan

    AlSayed Alarabi Sallam

Authors
  1. Shereen M. Assaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aya M. Ghanem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shayma’a A. Alhaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Enam A. Khalil
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. AlSayed Alarabi Sallam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, Assaf S.M., and Sallam A.A.; Methodology, Assaf S.M., Khalil E.A., and Sallam A.A.; validation, Assaf S.M., Ghanem A.M., and Sallam A.A.; formal analysis, Ghanem A.M.; investigation, Ghanem A.M. and Alhaj, S.A.; resources, Ghanem A.M. and Alhaj S.A.; data curation, Assaf S.M., Ghanem A.M., and Sallam A.A.; writing – original draft preparation, Assaf S.M.; Writing – Review & Editing, Assaf S.M., Ghanem A.M., Sallam A.A.; visualization, Ghanem A.M.; supervision, Assaf A.A., Sallam A.A., and Khalil E.A.; project administration, Assaf S.M. and Sallam A.A.; funding acquisition, Assaf S.M.

Corresponding author

Correspondence to Shereen M. Assaf.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

SEM images of the Strat-M membrane: (A) before permeation study and after (B) one week and (C) two weeks of the permeation study at 2500x magnification power. (GIF 86 kb)

ESM 2

Two-week in vitro permeation profiles of TMS from P9 after storing at 5 °C (refrigerated), 30 °C/ 60% RH (30 degrees), and 40 °C/ 75% RH (40 degrees), through Strat-M® membrane into phosphate buffer (pH 6.8) at 32 ± 1 oC, compared with its permeation from a freshly prepared patch (mean ± RSD, n=3). (GIF 12 kb)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Assaf, S.M., Ghanem, A.M., Alhaj, S.A. et al. Formulation and Evaluation of Eudragit® RL Polymeric Double Layer Films for Prolonged-Release Transdermal Delivery of Tamsulosin Hydrochloride. AAPS PharmSciTech 23, 210 (2022). https://doi.org/10.1208/s12249-022-02358-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-022-02358-x

Keywords

search

Navigation