Skip to main content

Advertisement

Log in

Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Ketoprofen (KP) is a widely used transdermal non-steroidal anti-inflammatory drug. However, increasing number of adverse effect case reports suggests that KP transdermal formulation can cause photoallergic reaction. The photoallergic potential of KP is attributable to the instability of KP under UV/visible light and subsequent formation of reactive degradation products. In this study, we investigated whether the inclusion of titanium dioxide (TiO2), a well-known mineral sunscreen agent, in the KP transdermal patch can prevent the photodegradation of KP and ultimately, can reduce photoallergic reaction. TiO2 inclusion in fabric backing effectively decreased the UV transmission through fabric patch throughout all UVA region from 320 to 380 nm and consistently, KP patch with TiO2 exhibited significantly increased photostability of KP. This enhanced photostability of KP resulted in reduced generation of photodegradation product as determined by HPLC–UV analysis. In a good accordance with these in vitro results, photosensitization test in guinea pig in vivo demonstrated low photoallergic reactions of KP patch with TiO2 compared to KP patch without TiO2, indeed. This study demonstrated that KP transdermal patch with TiO2-included backing can provide with improved photostability and photosafety over conventional fabric KP patch.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alastair K, James F (2010) Photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed 26:56–65

    Article  Google Scholar 

  • Albes B, Marguery MC, Schwarze HP, Journe F, Loche F, Bazex J (2000) Prolonged photosensitivity following contact photoallergy to ketoprofen. Dermatology 201:171–174

    Article  CAS  PubMed  Google Scholar 

  • Bagheri H, Lhiaubet V, Montastruc JL, Chouini-Lalanne N (2000) Photosensitivity to ketoprofen: mechanisms and pharmacoepidemiological data. Drug Saf 22:339–349

    Article  CAS  PubMed  Google Scholar 

  • Devleeschouwer V, Roelandts R, Garmyn M, Goossens A (2008) Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Derm 58:159–166

    Article  CAS  PubMed  Google Scholar 

  • Diaz RL, Gardeazabal J, Manrique P, Raton JA, Urrutia I, Rodriguez-Sasiain JM, Aguirre C (2006) Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use. Contact Derm 54:239–243

    Article  CAS  PubMed  Google Scholar 

  • Dondi D, Albini A, Serpone N (2006) Interactions between different solar UVB/UVA filters contained in commercial suncreams and consequent loss of UV protection. Photochem Photobiol Sci 5:835–843

    Article  CAS  PubMed  Google Scholar 

  • Emmert B, Schauder S, Palm H, Hallier E, Emmert S (2007) Disabling work-related persistent photosensitivity following photoallergic contact dermatitis from chlorpromazine and olaquindox in a pig breeder. Ann Agric Environ Med 14:329–333

    CAS  PubMed  Google Scholar 

  • Erhard HZ, Percy L, Norbert N (2009) Phototoxic and photoallergic reactions. J Dtsch Dermatol Ges 7:643–648

    Google Scholar 

  • Gerberick GF, Ryan CA (1989) Contact photoallergy testing of sunscreens in guinea pigs. Contact Derm 20:251–259

    Article  CAS  PubMed  Google Scholar 

  • Heo SK, Cho J, Cheon JW, Choi MK, Im DS, Kim JJ, Choi YG, Jeon do Y, Chung SJ, Shim CK, Kim DD (2008) Pharmacokinetics and pharmacodynamics of ketoprofen plasters. Biopharm Drug Dispos 29:37–44

    Article  CAS  PubMed  Google Scholar 

  • Hinds M, Isaksson ME, Persson L, Zimersson E, Bruze M (2004) Photoallergic contact dermatitis from ketoprofen induced by drug-contaminated personal objects. J Am Acad Dermatol 50:215–219

    Article  Google Scholar 

  • Kantor TG (1986) Ketoprofen: a review of its pharmacologic and clinical properties. Pharmacotherapy 6:93–103

    CAS  PubMed  Google Scholar 

  • Kligman AM, Basketter DA (1995) A critical commentary and updating of the guinea pig maximization test. Contact Derm 32:129–134

    Article  CAS  PubMed  Google Scholar 

  • Lee BS, Choi YG, Son WC, Jung KM, Kim JJ, Kim BH (2007) Ketoprofen: experimental overview of dermal toxicity. Arch Toxicol 81:743–748

    Article  CAS  PubMed  Google Scholar 

  • Loden M, Akerstrom U, Lindahl K, Berne B (2004) Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic approach and excised skin penetration. Int J Pharm 284:23–30

    Article  CAS  PubMed  Google Scholar 

  • Mazieres B (2005) Topical ketoprofen patch. Drugs R D 6:337–344

    Article  CAS  PubMed  Google Scholar 

  • Nakazawa T, Shimo T, Chikamatsu N, Igarashi T, Nagata O, Yamamoto M (2006) Study on the mechanism of photosensitive dermatitis caused by ketoprofen in the guinea pig. Arch Toxicol 80:442–448

    Article  CAS  PubMed  Google Scholar 

  • Noize P, Benard-Laribiere A, Aulois-Griot M, Moore N, Miremont-Salame G, and Haramburu F (2010) Cutaneous adverse effects of ketoprofen for topical use: clinical patterns and costs. Am J Clin Dermatol 11:131–136

    Google Scholar 

  • Paolino D, Ventura CA, Nistico S, Puglisi G, Fresta M (2002) Lecithin microemulsions for the topical administration of ketoprofen: percutaneous adsorption through human skin and in vivo human skin tolerability. Int J Pharm 244:21–31

    Article  CAS  PubMed  Google Scholar 

  • Rhee YS, Choi JG, Park ES, Chi SC (2001) Transdermal delivery of ketoprofen using microemulsions. Int J Pharm 228:161–170

    Article  CAS  PubMed  Google Scholar 

  • Serrano G, Fortea JM, Latasa JM, Millan F, Janes C, Bosca F, Miranda MA (1992) Photosensitivity induced by fibric acid derivatives and its relation to photocontact dermatitis to ketoprofen. J Am Acad Dermatol 27:204–208

    Article  CAS  PubMed  Google Scholar 

  • Shinkai N, Korenaga K, Mizu H, Yamauchi H (2008) Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats. J Control Release 131:107–112

    Article  CAS  PubMed  Google Scholar 

  • Tonnesen HH (2001) Formulation and stability testing of photolabile drugs. Int J Pharm 225:1–14

    Article  CAS  PubMed  Google Scholar 

  • Wakefield G, Stott J (2007) Photostabilization of organic UV-absorbing and anti-oxidant cosmetic components in formulations containing micronized manganese-doped titanium oxide. Int J Cosmet Sci 29:139

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kang Choon Lee or Kyung-Min Lim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, YG., Lee, J.H., Bae, IH. et al. Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch. Arch Toxicol 85, 219–226 (2011). https://doi.org/10.1007/s00204-010-0569-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-010-0569-x

Keywords

Navigation