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Cold Flow Evaluation in Transdermal Drug Delivery Systems by Measuring the Width of the Oozed Adhesive

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Abstract

The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed adhesive around the original sample was suggested to be an index that properly describes the relationship between the load per unit area and the extent of CF. Further, it was clarified that the average CF width over the entire circumference of the sample was the same whether the samples were round or square as long as the sample area and load were the same. We also observed a linear relationship between the CF width and the aspect ratio of oval and rectangular samples. These results indicated that the CF properties of typical TDDS products lacking CF-proof processing at the edges could be determined by testing samples cut from the product rather than the whole TDDS patch. The proposed width measuring method was simple and useful for optimizing the composition of the adhesive and for testing the quality of the product.

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References

  1. Van Buskirk GA, Arsulowicz D, Basu P, Block L, Cai B, Cleary GW, et al. Passive transdermal systems whitepaper incorporating current chemistry, manufacturing and controls (CMC) development principles. AAPS PharmSciTech. 2012;13:218–30. https://doi.org/10.1208/s12249-011-9740-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Parekh D, Miller MA, Borys D, Patel PR, Levsky ME. Transdermal patch medication delivery systems and pediatric poisonings, 2002-2006. Clin Pediatr. 2008;47:659–63. https://doi.org/10.1177/0009922808315211.

    Article  Google Scholar 

  3. Woolf A, Burkhart K, Caraccio T, Litovitz T. Childhood poisoning involving transdermal nicotine patches. Pediatrics. 1997;99:E4. https://doi.org/10.1542/peds.99.5.e4.

    Article  CAS  PubMed  Google Scholar 

  4. Yerasi AB, Butts JD, Butts JD. Disposal of used fentanyl patches. Am J Health-Syst Ph. 1997;54:85–6. https://doi.org/10.1093/ajhp/54.1.85.

    Article  CAS  Google Scholar 

  5. United States Food and Drug Administration. Fentanyl patch can be deadly to children. 2012. https://www.fda.gov/consumers/consumer-updates/fentanyl-patch-can-be-deadly-children. Accessed 20 Aug 2019.

  6. Banerjee S, Chattopadhyay P, Ghosh A, Datta P, Veer V. Aspect of adhesives in transdermal drug delivery systems. Int J Adhes Adhes. 2014;50:70–84. https://doi.org/10.1016/j.ijadhadh.2014.01.001.

    Article  CAS  Google Scholar 

  7. European Medicines Agency. Guideline on quality of transdermal patches. 2014. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-quality-transdermal-patches_en.pdf. Accessed 20 Aug 2019.

  8. Standard test method for time to failure of pressure sensitive articles under sustained shear loading. ASTM D6463/D6463M-06. West Conshohocken, PA: ASTM International; 2012.

  9. Cilurzo F, Gennari CGM, Minghetti P. Adhesive properties: a critical issue in transdermal patch development. Expert Opin Drug Deliv. 2012;9:33–45. https://doi.org/10.1517/17425247.2012.637107.

    Article  CAS  PubMed  Google Scholar 

  10. Hui CY, Liu Z, Minsky H, Creton C, Ciccotti M. Mechanics of an adhesive tape in a zero degree peel test: effect of large deformation and material nonlinearity. Soft Matter. 2018;14:9681–92. https://doi.org/10.1039/c8sm01731j.

    Article  CAS  PubMed  Google Scholar 

  11. Venna D, Khan AB. Role of adhesives in transdermal drug delivery: a review. Int J Pharm Sci Res. 2012;3:3559–64. https://doi.org/10.13040/IJPSR.0975-8232.3(10).3559-64.

    Article  CAS  Google Scholar 

  12. Minghetti P, Cilurzo F, Casiraghi A. Measuring adhesive performance in transdermal delivery systems. Am J Drug Deliv. 2004;2:193–206. https://doi.org/10.2165/00137696-200402030-00004.

    Article  CAS  Google Scholar 

  13. Pemberton-Pigott N, Burger G, Wasylyshyn DA. Performance of pressure-sensitive adhesive tapes under different strain rates. Plastic Decorating. 2015. https://plasticsdecorating.com/articles/2015/performance-of-pressure-sensitive-adhesive-tapes-under-different-strain-rates/. Accessed 20 Aug 2019.

  14. Wokovich AM, Strasinger C, Kessler J, Cai B, Westenberger B, Rhee MJ, et al. Cold flow measurement of transdermal drug delivery systems (TDDS). Int J Adhes Adhes. 2015;59:71–6. https://doi.org/10.1016/j.ijadhadh.2015.02.002.

    Article  CAS  Google Scholar 

  15. Krishnaiah YSR, Katragadda U, Khan MA. Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems. J Pharm Sci. 2014;103:1433–42. https://doi.org/10.1002/jps.23915.

    Article  CAS  PubMed  Google Scholar 

  16. Krishnaiah YSR, Yang Y, Hunt RL, Khan MA. Cold flow of estradiol transdermal systems: influence of drug loss on the in vitro flux and drug transfer across human epidermis. Int J Pharm. 2014;477:73–80. https://doi.org/10.1016/j.ijpharm.2014.10.013.

    Article  CAS  PubMed  Google Scholar 

  17. Wolff HM, Dodou IK. Investigations on the viscoelastic performance of pressure sensitive adhesives in drug-in-adhesive type transdermal films. Pharm Res. 2014;31:2186–202. https://doi.org/10.1007/s11095-014-1318-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Krishnaiah YSR, Pavurala N, Yang Y, Manda P, Katragadda U, Yang Y, et al. In vitro drug transfer due to drug retention in human epidermis pretreated with application of marketed estradiol transdermal systems. AAPS PharmSciTech. 2017;18:2131–40. https://doi.org/10.1208/s12249-016-0694-9.

    Article  CAS  PubMed  Google Scholar 

  19. Bandyopadhyay A. Transdermal drug delivery system-quality by design approach. J Bioanal Biomed. 2017;9:217–9. https://doi.org/10.4172/1948-593X.1000181.

    Article  CAS  Google Scholar 

  20. Markarian J. Critical parameters in transdermal patch manufacturing. Pharm Technol. 2017;41:44–5 http://www.pharmtech.com/critical-parameters-transdermal-patch-manufacturing.

    CAS  Google Scholar 

  21. Schalau GK II, Bobenrieth A, Huber RO, Nartker LS, Thomas X. Silicone adhesives in medical applications. Applied Adhesive Bonding in Science and Technology. 2017. https://www.intechopen.com/books/applied-adhesive-bonding-in-science-and-technology/silicone-adhesives-in-medical-applications. Accessed 20 Aug 2019.

  22. Greth M, Karabiyik G. The criticality of adhesive selection for optimal transdermal drug delivery systems. On drug delivery. 2016; 65:23–5. Frederick Furness Publishing Ltd. https://www.ondrugdelivery.com/wp-content/uploads/2016/03/Skin-Drug-Delivery-Dermal-Transdermal-Microneedles-ONdrugDelivery-Issue-65.pdf. Accessed 20 Aug 2019.

  23. Mahavir S, Rashmi S. Transdermal drug delivery adhesion as a critical parameter. Int Res J Pharm. 2013;4:16–21. https://doi.org/10.7897/2230-8407.04905.

    Article  Google Scholar 

  24. Wokovich AM, Prodduturi S, Doub WH, Hussain AS, Buhse LF. Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute. Eur J Pharm Biopharm. 2006;64:1–8. https://doi.org/10.1016/j.ejpb.2006.03.009.

    Article  CAS  PubMed  Google Scholar 

  25. Standard test method for conducting creep, creep-rupture, and stress-rupture tests of metallic materials. ASTM E139-11. West Conshohocken, PA: ASTM International; 2018.

  26. Standard test methods for tensile, compressive, and flexural creep and creep rupture of plastics. ASTM D2990-17. West Conshohocken, PA: ASTM International; 2017.

  27. Ahmad Z, Ansell M, Smedley D, Tahir P. Creep behavior of epoxy-based adhesive reinforced with nanoparticles for bonded-in timber connection. J Mater Civ Eng. 2012;24:825–31. https://doi.org/10.1061/(ASCE)MT.1943-5533.0000453.

    Article  CAS  Google Scholar 

  28. Paul CW. Pressure-sensitive adhesives (PSAs). In: Lucas FMS, Öchsner A, Adams RD, editors. Handbook of adhesion technology. Berlin, Heidelberg: Springer; 2011. p. 341–72. https://doi.org/10.1007/978-3-642-01169-6_15.

    Chapter  Google Scholar 

  29. Ahearne M, Yang Y, El Haj AJ, Then KY, Liu K. Characterizing the viscoelastic properties of thin hydrogel-based constructs for tissue engineering applications. J R Soc Interface. 2005;2:455–63. https://doi.org/10.1098/rsif.2005.0065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wasserman S, Dodiuk H, Kenig S. Shear creep behavior of elastomeric adhesives. Int J Adhes Adhes. 1992;12:257–61. https://doi.org/10.1016/0143-7496(92)90063-2.

    Article  CAS  Google Scholar 

  31. Singh V, Misra A, Parthasarathy R, Ye Q, Park J, Spencer P. Mechanical properties of methacrylate-based model dentin adhesives: effect of loading rate and moisture exposure. J Biomed Mater Res B Appl Biomater. 2013;101:1437–43. https://doi.org/10.1002/jbm.b.32963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ju BF, Liu K. Characterizing viscoelastic properties of thin elastomeric membrane. Mech Mater. 2002;34:485–91. https://doi.org/10.1016/S0167-6636(02)00176-X.

    Article  Google Scholar 

  33. Kohyama K, Ishihara S, Nkauma M, Funami T. Compression test of soft food gels using a soft machine with an artificial tongue. Foods. 2019;8:E182. https://doi.org/10.3390/foods8060182.

    Article  CAS  PubMed  Google Scholar 

  34. Ikeda S, Sangu T, Nishinari K. Comparative studies on fracture characteristics of food gels subjected to uniaxial compression and torsion. Food Sci Technol Res. 2003;9:372–7. https://doi.org/10.3136/fstr.9.372.

    Article  Google Scholar 

  35. Tang J, Tung MA, Lelievre J, Zeng Y. Stress-strain relationships for gellan gels in tension, compression and torsion. J Food Eng. 1997;31:511–29. https://doi.org/10.1016/S0260-8774(96)00087-8.

    Article  Google Scholar 

  36. Goossens RHM, Snijders CJ, Hoek van Dijke GA, den Ouden AH. A new instrument for the measurement of forces on beds and seats. 1993;15:409–12. https://doi.org/10.1016/0141-5425(93)90078-D.

    Article  CAS  Google Scholar 

  37. Nakashima A, Nakajima K. Study on the resiliency of mattresses. Reports of the science of living (Osaka City University). 1963;11:39–46. http://dlisv03.media.osaka-cu.ac.jp/il/meta_pub/G0000438repository_111H0000001-11-5.

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Acknowledgments

The authors would like to thank 3M Japan Ltd. for providing pharmaceutical films.

Funding

This research was supported by the Japan Agency for Medical Research and Development under Grant Number JP17mk0101080-19mk0101082 and by the Pharmaceutical and Medical Device Regulatory Science Society of Japan under a grant called the 2017 Research Report of “Research on the tests for Japanese Pharmacopoeia.”

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Authors and Affiliations

  1. Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan

    Tamaki Miyazaki, Hitomi Kanno, Eiichi Yamamoto, Daisuke Ando, Ken-ich Izutsu & Yukihiro Goda

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  1. Tamaki Miyazaki
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Correspondence to Tamaki Miyazaki.

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Miyazaki, T., Kanno, H., Yamamoto, E. et al. Cold Flow Evaluation in Transdermal Drug Delivery Systems by Measuring the Width of the Oozed Adhesive. AAPS PharmSciTech 21, 120 (2020). https://doi.org/10.1208/s12249-020-01661-9

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