Skip to main content

Advertisement

SpringerLink
Log in

Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations

  • Review Article
  • Novel Approaches for Cutaneous Pharmacokinetics
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Novel formulations are developed for dermatological applications to address a wide range of patient needs and therapeutic challenges. By pushing the limits of pharmaceutical technology, these formulations strive to provide safer, more effective, and patient-friendly solutions for dermatological concerns, ultimately improving the overall quality of dermatological care. The article explores the different types of novel dermatological formulations, including nanocarriers, transdermal patches, microsponges, and microneedles, and the techniques involved in the cutaneous pharmacokinetics of these innovative formulations. Furthermore, the significance of knowing cutaneous pharmacokinetics and the difficulties faced during pharmacokinetic assessment have been emphasized. The article examines all the methods employed for the pharmacokinetic evaluation of novel dermatological formulations. In addition to a concise overview of earlier techniques, discussions on novel methodologies, including tape stripping, in vitro permeation testing, cutaneous microdialysis, confocal Raman microscopy, and matrix-assisted laser desorption/ionization mass spectrometry have been conducted. Emerging technologies like the use of microfluidic devices for skin absorption studies and computational models for predicting drug pharmacokinetics have also been discussed. This article serves as a valuable resource for researchers, scientists, and pharmaceutical professionals determined to enhance the development and understanding of novel dermatological drug products and the complex dynamics of cutaneous pharmacokinetics.

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

Similar content being viewed by others

References

  1. Leite-Silva VR, De Almeida MM, Fradin A, Grice JE, Roberts MS. Delivery of drugs applied topically to the skin. Expert Rev Dermatol. 2012;7(4):383–97.

    CAS  Google Scholar 

  2. Chauhan L, Gupta S. Creams: A review on classification, preparation methods, evaluation and its applications. J Drug Deliv Ther. 2020;10(5):281–9.

    Google Scholar 

  3. Espuelas S. Conventional formulations and emerging delivery systems for the topical treatment of cutaneous leishmaniasis. Ther Deliv. 2015;6(2):101–3.

    CAS  PubMed  Google Scholar 

  4. Das Kurmi B, Tekchandani P, Paliwal R, Rai PS. Transdermal drug delivery: opportunities and challenges for controlled delivery of therapeutic agents using nanocarriers. Curr Drug Metab. 2017;18(5):481–95.

    CAS  Google Scholar 

  5. Vitorino C, Sousa J, Pais A. Overcoming the skin permeation barrier: Challenges and opportunities. Curr Phar Des. 2015;21(20):2698–712.

    CAS  Google Scholar 

  6. Singhal M, Lapteva M, Kalia YN. Formulation challenges for 21st century topical and transdermal delivery systems. Expert Opin Drug Deliv. 2017;14(6):705–8.

    CAS  PubMed  Google Scholar 

  7. Jain AK, Jain S, Abourehab MA, Mehta P, Kesharwani P. An insight on topically applied formulations for management of various skin disorders. J Biomater Sci Polym Ed. 2022;33(18):2406–32.

    CAS  PubMed  Google Scholar 

  8. Rapalli VK, Sharma S, Roy A, Alexander A, Singhvi G. Solid lipid nanocarriers embedded hydrogel for topical delivery of apremilast: In-vitro, ex-vivo, dermatopharmacokinetic and anti-psoriatic evaluation. J Drug Deliv Sci Technol. 2021;63:102442.

    CAS  Google Scholar 

  9. Schurad B, Koch C, Schug B, Morte A, Vaqué A, De la Torre R, Iniesta M. Comparative bioavailability study of a novel multi-day patch formulation of rivastigmine (twice weekly) with Exelon® transdermal patch (Daily)-A randomized clinical trial. Curr Alzheimer Res. 2022;19(7):541.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Juhaščik M, Kováčik A, Huerta-Ángeles G. Recent advances of hyaluronan for skin delivery: From structure to fabrication strategies and applications. Polymers. 2022;14(22):4833.

    PubMed  PubMed Central  Google Scholar 

  11. Altamimi MA, Hussain A, Imam SS, Alshehri S, Singh SK, Webster TJ. Transdermal delivery of isoniazid loaded elastic liposomes to control cutaneous and systemic tuberculosis. J Drug Deliv Sci Technol. 2020;59:101848.

    CAS  Google Scholar 

  12. Franzé S, Marengo A, Stella B, Minghetti P, Arpicco S, Cilurzo F. Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration. Int J Pharm. 2018;535(1–2):333–9.

    PubMed  Google Scholar 

  13. Jain H, Geetanjali D, Dalvi H, Bhat A, Godugu C, Srivastava S. Liposome mediated topical delivery of ibrutinib and curcumin as a synergistic approach to combat imiquimod induced psoriasis. J Drug Deliv Sci Technol. 2022;68:103103.

    CAS  Google Scholar 

  14. Santos GA, Angelo T, Andrade LM, Silva SM, Magalhães PO, Cunha-Filho M, Gelfuso GM, Taveira SF, Gratieri T. The role of formulation and follicular pathway in voriconazole cutaneous delivery from liposomes and nanostructured lipid carriers. Colloids Surf B. 2018;170:341–6.

    CAS  Google Scholar 

  15. Yu YQ, Yang X, Wu XF, Fan YB. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: Novel strategies for effective transdermal applications. Front Bioeng Biotechnol. 2021;9:646554.

    PubMed  PubMed Central  Google Scholar 

  16. Güngör S, Kahraman E. Nanocarriers mediated cutaneous drug delivery. Eur J Pharm Sci. 2021;158:105638.

    PubMed  Google Scholar 

  17. Quartier J, Lapteva M, Boulaguiem Y, Guerrier S, Kalia YN. Polymeric micelle formulations for the cutaneous delivery of sirolimus: A new approach for the treatment of facial angiofibromas in tuberous sclerosis complex. Int J Pharm. 2021;604:120736.

    CAS  PubMed  Google Scholar 

  18. Balzus B, Sahle FF, Hönzke S, Gerecke C, Schumacher F, Hedtrich S, Kleuser B, Bodmeier R. Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium. Eur J Pharm Biopharm. 2017;115:122–30.

    CAS  PubMed  Google Scholar 

  19. Argenta DF, Martelli SM, Caon T. Dendrimer as a platform for drug delivery in the skin. Mater Biomed Eng 2019:331-367.

  20. Borowska K, Wołowiec S, Rubaj A, Głowniak K, Sieniawska E, Radej S. Effect of polyamidoamine dendrimer G3 and G4 on skin permeation of 8-methoxypsoralene—In vivo study. Int J Pharm. 2012;426(1–2):280–3.

    CAS  PubMed  Google Scholar 

  21. Ybarra DE, Calienni MN, Ramirez LF, Frias ET, Lillo C, del Valle Alonso S, Montanari J, Alvira FC. Vismodegib in PAMAM-dendrimers for potential theragnosis in skin cancer. OpenNano. 2022;7:100053.

    Google Scholar 

  22. Rai VK, Mishra N, Yadav KS, Yadav NP. Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications. J Contr Rel. 2018;270:203–25.

    CAS  Google Scholar 

  23. Fukumori C, Branco PC, Barreto T, Ishida K, Lopes LB. Development and cytotoxicity evaluation of multiple nanoemulsions for oral co-delivery of 5-fluorouracil and short chain triglycerides for colorectal cancer. Eur J Pharm Sci. 2023;187:106465.

    CAS  PubMed  Google Scholar 

  24. Amoozegar H, Ghaffari A, Keramati M, Ahmadi S, Dizaji S, Moayer F, Akbarzadeh I, Abazari M, Bakhshandeh H. A novel formulation of simvastatin nanoemulsion gel for infected wound therapy: In vitro and in vivo assessment. J Drug Deliv Sci Technol. 2022;72:103369.

    CAS  Google Scholar 

  25. Szumała P, Macierzanka A. Topical delivery of pharmaceutical and cosmetic macromolecules using microemulsion systems. Int J Pharm. 2022;615:121488.

    PubMed  Google Scholar 

  26. Pepe D, Phelps J, Lewis K, DuJack J, Scarlett K, Jahan S, Bonnier E, Milic-Pasetto T, Hass MA, Lopes LB. Decylglucoside-based microemulsions for cutaneous localization of lycopene and ascorbic acid. Int J Pharm. 2012;434(1–2):420–8.

    CAS  PubMed  Google Scholar 

  27. McGuckin MB, Wang J, Ghanma R, Qin N, Palma SD, Donnelly RF, Paredes AJ. Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. J Contr Release. 2022;345:334–53.

    CAS  Google Scholar 

  28. Xiang H, Xu S, Zhang W, Li Y, Zhou Y, Miao X. Skin permeation of curcumin nanocrystals: Effect of particle size, delivery vehicles, and permeation enhancer. Colloids and Surfaces B: Biointerfaces. 2023;224:113203.

    CAS  PubMed  Google Scholar 

  29. Bathe R, Kapoor R. Transdermal drug delivery system: Formulation, development and evaluation-An overview. Drug Deliv. 2015;6:7–12.

    Google Scholar 

  30. Phatale V, Vaiphei KK, Jha S, Patil D, Agrawal M, Alexander A. Overcoming skin barriers through advanced transdermal drug delivery approaches. J Contr Rel. 2022;351:361–80.

    CAS  Google Scholar 

  31. Joshi N, Machekposhti SA, Narayan RJ. Evolution of transdermal drug delivery devices and novel microneedle technologies: A historical perspective and review. JID Innovations. 2023;3.

    PubMed  PubMed Central  Google Scholar 

  32. Wang L, Pang Y, Zheng Q, Ruan J, Fang L. Development of mabuterol transdermal patch: Molecular mechanism study of ion-pair improving patch stability. Int J Pharm. 2023;644:123302.

    CAS  PubMed  Google Scholar 

  33. Sabri AH, Ogilvie J, Abdulhamid K, Shpadaruk V, McKenna J, Segal J, Scurr DJ, Marlow M. Expanding the applications of microneedles in dermatology. Eur J Pharm Biopharm. 2019;140:121–40.

    PubMed  Google Scholar 

  34. Jain AK, Lee CH, Gill HS. 5-Aminolevulinic acid coated microneedles for photodynamic therapy of skin tumors. J Control Rel. 2016;239:72–81.

    CAS  Google Scholar 

  35. Vemulapalli V, Yang Y, Friden PM, Banga AK. Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate. J Pharm Pharmacol. 2008;60(1):27–33.

    CAS  PubMed  Google Scholar 

  36. Jiang X, Wang S, Zhang L, Jiang X, Gou M. Lidocaine hydrochloride loaded isomaltulose microneedles for efficient local anesthesia of the skin. Chinese Chem Lett. 2023;35:108686.

    Google Scholar 

  37. Dali P, Shende P. Use of 3D applicator for intranasal microneedle arrays for combinational therapy in migraine. Int J Pharm. 2023;635:122714.

    CAS  PubMed  Google Scholar 

  38. Men Z, Su T, Tang Z, Liang J, Shen T. Tacrolimus nanocrystals microneedle patch for plaque psoriasis. Int J Pharm. 2022;627:122207.

    CAS  PubMed  Google Scholar 

  39. Liu Y, Zhang Z, Wang C, Xie X, Ma Y, Wang Y. Biodegradable and dissolvable resveratrol nanocrystals non-silicon microneedles for transdermal drug delivery. J Drug Deliv Sci Technol. 2023;86:104653.

    CAS  Google Scholar 

  40. Anjani QK, Pandya AK, Demartis S, Domínguez-Robles J, Moreno-Castellanos N, Li H, Gavini E, Patravale VB, Donnelly RF. Liposome-loaded polymeric microneedles for enhanced skin deposition of rifampicin. Int J Pharm. 2023;646:123446.

    CAS  PubMed  Google Scholar 

  41. Demartis S, Anjani QK, Volpe-Zanutto F, Paredes AJ, Jahan SA, Vora LK, Donnelly RF, Gavini E. Trilayer dissolving polymeric microneedle array loading Rose Bengal transfersomes as a novel adjuvant in early-stage cutaneous melanoma management. Int J Pharm. 2022;627:122217.

    CAS  PubMed  Google Scholar 

  42. Abd-El-Azim H, Abbas H, El Sayed NS, Fayez AM, Zewail M. Non-invasive management of rheumatoid arthritis using hollow microneedles as a tool for transdermal delivery of teriflunomide loaded solid lipid nanoparticles. Int J Pharm. 2023;644:123334.

    CAS  PubMed  Google Scholar 

  43. Kapoor Y, Milewski M, Dick L, Zhang J, Bothe JR, Gehrt M, Manser K, Nissley B, Petrescu I, Johnson P, Burton S. Coated microneedles for transdermal delivery of a potent pharmaceutical peptide. Biomed Microdev. 2020;22:7.

    CAS  Google Scholar 

  44. Mahant S, Kumar S, Nanda S, Rao R. Microsponges for dermatological applications: perspectives and challenges. Asian J Pharm Sci. 2020;15(3):273–91.

    PubMed  Google Scholar 

  45. Jelvehgari M, Siahi-Shadbad MR, Azarmi S, Martin GP, Nokhodchi A. The microsponge delivery system of benzoyl peroxide: Preparation, characterization and release studies. Int J Pharm. 2006;308(1–2):124–32.

    CAS  PubMed  Google Scholar 

  46. Kumar PM, Ghosh A. Development and evaluation of silver sulfadiazine loaded microsponge based gel for partial thickness (second degree) burn wounds. Eur J Pharm Sci. 2017;96:243–54.

    CAS  PubMed  Google Scholar 

  47. Li SS, Li GF, Liu L, Jiang X, Zhang B, Liu ZG, Li XL, Weng LD, Zuo T, Liu Q. Evaluation of paeonol skin-target delivery from its microsponge formulation: In vitro skin permeation and in vivo microdialysis. PloS one. 2013;8(11):e79881.

    PubMed  PubMed Central  Google Scholar 

  48. Lee EH, Lim SJ, Lee MK. Chitosan-coated liposomes to stabilize and enhance transdermal delivery of indocyanine green for photodynamic therapy of melanoma. Carbohydrate polymers. 2019;224: 115143.

    CAS  PubMed  Google Scholar 

  49. El-Telbany DF, El-Telbany RF, Zakaria S, Ahmed KA, El-Feky YA. Formulation and assessment of hydroxyzine HCL solid lipid nanoparticles by dual emulsification technique for transdermal delivery. Biomed Pharmacother. 2021;143:112130.

    CAS  PubMed  Google Scholar 

  50. Mohammadi-Samani S, Salehi H, Entezar-Almahdi E, Masjedi M. Preparation and characterization of sumatriptan loaded solid lipid nanoparticles for transdermal delivery. J Drug Deliv Sci Technol. 2020;57:101719.

    CAS  Google Scholar 

  51. Chauhan MK, Sharma PK. Optimization and characterization of rivastigmine nanolipid carrier loaded transdermal patches for the treatment of dementia. Chem Phys Lipids. 2019;224:104794.

    CAS  PubMed  Google Scholar 

  52. Nayeem U, Garg A, Das AK, Shree N, Sultana Y, Ahmed S, Khan MA. Development and evaluation of the novel chitosan-based 1% clindamycin & 2.5% benzoyl peroxide transferosomal gel for topical acne treatment. J Drug Deliv Sci Technol. 2023;89:105002.

    CAS  Google Scholar 

  53. Alkilani AZ, Hamed R, Al-Marabeh S, Kamal A, Abu-Huwaij R, Hamad I. Nanoemulsion-based film formulation for transdermal delivery of carvedilol. J Drug Deliv Sci Technol. 2018;46:122–8.

    Google Scholar 

  54. Duangjit S, Rattanachithawat N, Opanasopit P, Ngawhirunpat T. Development and optimization of finasteride-cinnamon oil-loaded ethanol-free microemulsions for transdermal delivery. J Drug Deliv Sci Technol. 2022;69:103107.

    CAS  Google Scholar 

  55. Park C, Zuo J, Somayaji V, Lee BJ, Löbenberg R. Development of a novel cannabinoid-loaded microemulsion towards an improved stability and transdermal delivery. Int J Pharm. 2021;604:120766.

    CAS  PubMed  Google Scholar 

  56. Mudhol S, Peddha MS. Development of capsaicin loaded nanoparticles based microneedle patch for transdermal drug delivery. J Drug Deliv Sci Technol. 2023;80:104120.

    CAS  Google Scholar 

  57. Tosun NG, Tayhan SE, Gokce İ, Alkan C. Doxorubicin-loaded mPEG-pPAd-mPEG triblock polymeric nanoparticles for drug delivery systems: Preparation and in vitro evaluation. J Mol Struct. 2023;1291:135959.

    Google Scholar 

  58. Poustforoosh A, Hashemipour H, Pardakhty A, Pour MK. Preparation of nano-micelles of meloxicam for transdermal drug delivery and simulation of drug release: A computational supported experimental study. Canadian J Chem Eng. 2022;100(11):3428–36.

    CAS  Google Scholar 

  59. Kirkby M, Sabri AB, Scurr DJ, Moss GP. Dendrimer-mediated permeation enhancement of chlorhexidine digluconate: Determination of in vitro skin permeability and visualisation of dermal distribution. Eur J Pharm Biopharm. 2021;159:77–87.

    CAS  PubMed  Google Scholar 

  60. Wester RC, Maibach HI. Cutaneous pharmacokinetics: 10 steps to percutaneous absorption. Drug Metab Rev. 1983;14(2):169–205.

    CAS  PubMed  Google Scholar 

  61. Quantin P, Stricher M, Catoire S, Ficheux H, Egles C. Dermatokinetics: Advances and experimental models, focus on skin metabolism. Curr Drug Metab. 2022;23(5):340–54.

    CAS  PubMed  Google Scholar 

  62. Benson HA. Skin structure, function, and permeation. Topical and Transdermal Drug Delivery Principles Practice 2012:1-22.

  63. Calvery HO, Draize JH, Laug EP. The metabolism and permeability of normal skin. Physiol Rev. 1946;26(4):495–540.

    CAS  PubMed  Google Scholar 

  64. Rougier A, Lotte C, Maibach HI. In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: Predictive assessment by the stripping method. J Pharm Sci. 1987;76(6):451–4.

    CAS  PubMed  Google Scholar 

  65. Tur E, Maibach HI, Guy RH. Percutaneous penetration of methyl nicotinate at three anatomic sites: Evidence for an appendageal contribution to transport. Skin Pharmacol Physiol. 1991;4(4):230-4.66.

  66. Menon GK, Elias PM. The epidermal barrier and strategies for surmounting it: an overview. Skin Gene Ther. 2001:3-26.

  67. Jepps OG, Dancik Y, Anissimov YG, Roberts MS. Modeling the human skin barrier—Towards a better understanding of dermal absorption. Adv Drug Deliv Rev. 2013;65(2):152–68.

    CAS  PubMed  Google Scholar 

  68. Wohlrab J. Influence of keratolytics on cutaneous pharmacokinetics of glucocorticoids. JDDG Journal der Deutschen Dermatologischen Gesellschaft. 2021;19(4):554–61.

    PubMed  Google Scholar 

  69. Kienzler JL, Queille-Roussel C, Mugglestone C, Ortonne JP, Larnier C. Stratum corneum pharmacokinetics of the anti-fungal drug, terbinafine, in a novel topical formulation, for single-dose application in dermatophytoses. Curr Med Res Opin. 2007;23(6):1293–302.

    CAS  PubMed  Google Scholar 

  70. Wijnant GJ, Van Bocxlaer K, Fortes Francisco A, Yardley V, Harris A, Alavijeh M, Murdan S, Croft SL. Local skin inflammation in cutaneous leishmaniasis as a source of variable pharmacokinetics and therapeutic efficacy of liposomal amphotericin B. Antimicro Agents Chemother. 2018;62(10):10–128.

    Google Scholar 

  71. Korinth G, Wellner T, Schaller KH, Drexler H. Potential of the octanol–water partition coefficient (log P) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions. Toxicol Lett. 2012;215(1):49–53.

    CAS  PubMed  Google Scholar 

  72. Hafeez F, Maibach H. Do partition coefficients (liphophilicity/hydrophilicity) predict effects of occlusion on percutaneous penetration in vitro: A retrospective review. Cutaneous Ocular Toxicol. 2013;32(4):299–303.

    CAS  Google Scholar 

  73. Jornada DH, dos Santos Fernandes GF, Chiba DE, de Melo TR, dos Santos JL, Chung MC. The prodrug approach: A successful tool for improving drug solubility. Molecules. 2015;21(1):42.

    PubMed  PubMed Central  Google Scholar 

  74. Chen J, Bian J, Hantash BM, Albakr L, Hibbs DE, Xiang X, Xie P, Wu C, Kang L. Enhanced skin retention and permeation of a novel peptide via structural modification, chemical enhancement, and microneedles. Int J Pharm. 2021;606:120868.

    CAS  PubMed  Google Scholar 

  75. Liu C, Quan P, Fang L. Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive. Eur J Pharm Sci. 2016;93:437–46.

    CAS  PubMed  Google Scholar 

  76. Farahmand S, Maibach HI. Estimating skin permeability from physicochemical characteristics of drugs: A comparison between conventional models and an in vivo-based approach. Int J Pharm. 2009;375(1–2):41–7.

    CAS  PubMed  Google Scholar 

  77. Chantasart D, Chootanasoontorn S, Suksiriworapong J, Li KS. Investigation of pH influence on skin permeation behavior of weak acids using nonsteroidal anti-inflammatory drugs. J Pharm Sci. 2015;104(10):3459–70.

    CAS  PubMed  Google Scholar 

  78. Trivedi R, Umekar M, Kotagale N, Bonde S, Taksande J. Design, evaluation and in vivo pharmacokinetic study of a cationic flexible liposomes for enhanced transdermal delivery of pramipexole. J Drug Deliv Sci Technol. 2021;61:102313.

    CAS  Google Scholar 

  79. Yano T, Nakagawa A, Tsuji M, Noda K. Skin permeability of various non-steroidal anti-inflammatory drugs in man. Life Sci. 1986;39(12):1043–50.

    CAS  PubMed  Google Scholar 

  80. Hirakawa Y, Ueda H, Takata Y, Minamihata K, Wakabayashi R, Kamiya N, Goto M. Co-amorphous formation of piroxicam-citric acid to generate supersaturation and improve skin permeation. Eur J Pharm Sci. 2021;158:105667.

    CAS  PubMed  Google Scholar 

  81. Neupane R, Boddu SHS, Renukuntla J, Babu RJ, Tiwari AK. Alternatives to biological skin in permeation studies: Current trends and possibilities. Pharmaceutics. 2020;12(2):152.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kretsos K, Nitsche JM, Kasting GB. Distributed diffusion–clearance model for transient drug distribution within the skin. J Pharm Sci. 2004;93(11):2820–35.

    CAS  PubMed  Google Scholar 

  83. Supe S, Takudage P. Methods for evaluating penetration of drug into the skin: A review. Skin Res Technol. 2021;27(3):299–308.

    PubMed  Google Scholar 

  84. Bucks DA. Skin structure and metabolism: Relevance to the design of cutaneous therapeutics. Pharm Res. 1984;1:148–53.

    CAS  PubMed  Google Scholar 

  85. Kao J, Carver MP. Cutaneous metabolism of xenobiotics. Drug Metab Rev. 1990;22(4):363–410.

    CAS  PubMed  Google Scholar 

  86. Tabosa MA, Cordery SF, White KJ, Bunge AL, Guy RH, Delgado-Charro MB. Skin pharmacokinetics of diclofenac and co-delivered functional excipients. Int J Pharm. 2022;614:121469.

    CAS  PubMed  Google Scholar 

  87. Raza K, Singh B, Singla S, Wadhwa S, Garg B, Chhibber S, Katare OP. Nanocolloidal carriers of isotretinoin: Antimicrobial activity against Propionibacterium acnes and dermatokinetic modeling. Mol Pharm. 2013;10(5):1958–63.

    CAS  PubMed  Google Scholar 

  88. Erdő F, Hashimoto N, Karvaly G, Nakamichi N, Kato Y. Critical evaluation and methodological positioning of the transdermal microdialysis technique A review. J Contr Rel. 2016;233:147–61.

    Google Scholar 

  89. Iliopoulos F, Chapman A, Lane ME. A comparison of the in vitro permeation of 3‐O‐ethyl‐l‐ascorbic acid in human skin and in a living skin equivalent (LabSkin™). Int J Cosmet Sci. 2021;43(1):107-12.90.

  90. Agonia AS, Palmeira-de-Oliveira A, Cardoso C, Augusto C, Pellevoisin C, Videau C, Dinis-Oliveira RJ, Palmeira-de-Oliveira R. Reconstructed human epidermis: An alternative approach for in vitro bioequivalence testing of topical products. Pharmaceutics. 2022;14(8):1554.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Veitch D, Miller J, Raichura S, McKenna J. Skin biopsy. Br J Hospital Med. 2018;79(5):C78-80.

    Google Scholar 

  92. Laugier JP, Surber C, Bun H, Geiger JM, Wilhelm KP, Durand A, Maibach HI. Determination of acitretin in the skin, in the suction blister, and in plasma of human volunteers after multiple oral dosing. J Pharm Sci. 1994;83(5):623–8.

    CAS  PubMed  Google Scholar 

  93. Belson A, Schmidt T, Fernando D, Hardes K, Scott N, Brett S, Clark D, Oliveira JJ, Davis B, McHugh S, Stone J. Characterisation of the clinical and activated T cell response to repeat delayed-type hypersensitivity skin challenges in human subjects, with KLH and PPD, as a potential model to test T cell-targeted therapies. Inflamm Res. 2016;65:389–404.

    CAS  PubMed  Google Scholar 

  94. Hoppel M, Tabosa MA, Bunge AL, Delgado-Charro MB, Guy RH. Assessment of drug delivery kinetics to epidermal targets in vivo. The AAPS Journal. 2021;23:1–11.

    Google Scholar 

  95. Escobar-Chavez JJ, Merino-Sanjuán V, López-Cervantes M, Urban-Morlan Z, Piñón-Segundo E, Quintanar-Guerrero D, Ganem-Quintanar A. The tape-stripping technique as a method for drug quantification in skin. J Pharm Pharm Sci. 2008;11(1):104–30.

    CAS  PubMed  Google Scholar 

  96. Jui-Chen T, Weiner ND, Flynn GL, Ferry J. Properties of adhesive tapes used for stratum corneum stripping. Int J Pharm. 1991;72(3):227–31.

    Google Scholar 

  97. Weigmann HJ, Lademann J, Pelchrzim RV, Sterry W, Hagemeister T, Molzahn R, Schaefer M, Lindscheid M, Schaefer H, Shah VP. Bioavailability of clobetasol propionate–quantification of drug concentrations in the stratum corneum by dermatopharmacokinetics using tape stripping. Skin Pharmacol Appl Skin Physiol. 1999;12(1–2):46–53.

    CAS  PubMed  Google Scholar 

  98. Rath S, Kanfer I. In vitro–in vivo correlations (IVIVC) for predicting the clinical performance of metronidazole topical creams intended for local action. Pharmaceutics. 2023;15(1):268.

    PubMed  PubMed Central  Google Scholar 

  99. Wargniez W, Connétable S, Bourokba N, Dufour O, Nouveau S, Grégoire S. In-vivo tape stripping study with caffeine for comparisons on body sites, age and washing. Pharm Res. 2022;39(8):1935–44.

    CAS  PubMed  Google Scholar 

  100. Siddique MI, Katas H, Amin MC, Ng SF, Zulfakar MH, Jamil A. In-vivo dermal pharmacokinetics, efficacy, and safety of skin targeting nanoparticles for corticosteroid treatment of atopic dermatitis. Int J Pharm. 2016;507(1–2):72–82.

    CAS  PubMed  Google Scholar 

  101. Holmgaard R, Nielsen JB, Benfeldt E. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: Current state and future perspectives. Skin Pharmacol Physiol. 2010;23(5):225–43.

    CAS  PubMed  Google Scholar 

  102. Schmelz M, Luz O, Averbeck B, Bickel A. Plasma extravasation and neuropeptide release in human skin as measured by intradermal microdialysis. Neurosci Lett. 1997;230(2):117–20.

    CAS  PubMed  Google Scholar 

  103. Kuzma BA, Pence IJ, Ho A, Evans CL. Visualizing and quantifying pharmaceutical compounds within skin using coherent Raman scattering imaging. JoVE (Journal of Visualized Experiments). 2021;24(177):e63264.

    Google Scholar 

  104. Jung N, Namjoshi S, Mohammed Y, Grice JE, Benson HA, Raney SG, Roberts MS, Windbergs M. Application of confocal Raman microscopy for the characterization of topical semisolid formulations and their penetration into human skin ex vivo. Pharm Res. 2022;39(5):935–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Iliopoulos F, Goh CF, Haque T, Rahma A, Lane ME. Dermal delivery of diclofenac sodium—In vitro and in vivo studies. Pharmaceutics. 2022;14(10):2106.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Kichou H, Munnier E, Dancik Y, Kemel K, Byrne HJ, Tfayli A, Bertrand D, Soucé M, Chourpa I, Bonnier F. Estimating the analytical performance of Raman spectroscopy for quantification of active ingredients in human stratum corneum. Molecules. 2022;27(9):2843.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Xu F, Zhu J, Zhang Z, Li S, He Y, Dong Y, Zhan X. In vivo evaluation of the skin penetration and efficacy of ceramide nanomulsions by confocal Raman spectroscopy. 2023:Available at SSRN 4458382.

  108. Liu H, Pan Y, Xiong C, Han J, Wang X, Chen J, Nie Z. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for in situ analysis of endogenous small molecules in biological samples. TrAC Trends Anal Chem. 2022:116809.

  109. Rzagalinski I, Volmer DA. Quantification of low molecular weight compounds by MALDI imaging mass spectrometry–A tutorial review. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2017;1865(7):726-39.

  110. Bonnel D, Legouffe R, Eriksson AH, Mortensen RW, Pamelard F, Stauber J, Nielsen KT. MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles. Analytic Bioanal Chem. 2018;410:2815–28.

    CAS  Google Scholar 

  111. Handler AM, Pedersen GP, Nielsen KT, Janfelt C, Pedersen AJ, Clench MR. Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin. Eur J Pharm Biopharm. 2021;159:1–10.

    CAS  PubMed  Google Scholar 

  112. Lukács B, Bajza Á, Kocsis D, Csorba A, Antal I, Iván K, Laki AJ, Erdő F. Skin-on-a-chip device for ex vivo monitoring of transdermal delivery of drugs—Design, fabrication, and testing. Pharmaceutics. 2019;11(9):445.

    PubMed  PubMed Central  Google Scholar 

  113. Van der Schueren L, De Schoenmaker B, Kalaoglu ÖI, De Clerck K. An alternative solvent system for the steady state electrospinning of polycaprolactone. Eur Polymer J. 2011;47(6):1256–63.

    Google Scholar 

  114. Tárnoki-Zách J, Mehes E, Varga-Medveczky Z, Isai DG, Barany N, Bugyik E, Revesz Z, Paku S, Erdo F, Czirok A. Development and evaluation of a human skin equivalent in a semiautomatic microfluidic diffusion chamber. Pharmaceutics. 2021;13(6):910.

    PubMed  PubMed Central  Google Scholar 

  115. Fernandez-Carro E, Angenent M, Gracia-Cazaña T, Gilaberte Y, Alcaine C, Ciriza J. Modeling an optimal 3D skin-on-chip within microfluidic devices for pharmacological studies. Pharmaceutics. 2022;14(7):1417.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. McCarley KD, Bunge AL. Physiologically relevant two-compartment pharmacokinetic models for skin. J Pharm Sci. 2000;89(9):1212–35.

    CAS  PubMed  Google Scholar 

  117. Kattou P, Lian G, Glavin S, Sorrell I, Chen T. Development of a two-dimensional model for predicting transdermal permeation with the follicular pathway: Demonstration with a caffeine study. Pharm Res. 2017;34:2036–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Patel P, Schmieder S, Krishnamurthy K. Research techniques made simple: Drug delivery techniques, Part 2: Commonly used techniques to assess topical drug bioavailability. J Investig Dermatol. 2016;136(5):e43-9.

    CAS  PubMed  Google Scholar 

  119. Rapalli VK, Singhvi G. Dermato-pharmacokinetic: Assessment tools for topically applied dosage forms. Expert Opinion Drug Deliv. 2021;18(4):423–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Faculty of Pharmacy, and Research & Development Cell, Parul University, Waghodia, Vadodara, 391760, Gujarat, India

    Meenakshi Patel

  2. Department of Pharmaceutics, Krishna School of Pharmacy & Research, Drs. Kiran and Pallavi Patel Global University, Vadodara, 391243, Gujarat, India

    Ashwini Patel

  3. Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology (CHARUSAT), CHARUSAT Campus, Changa, 388 421, Gujarat, India

    Jagruti Desai & Swayamprakash Patel

Authors
  1. Meenakshi Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashwini Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jagruti Desai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Swayamprakash Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and supervision: Meenakshi Patel; writing original draft: Meenakshi Patel, Ashwini Patel, Jagruti Desai, and Swayamprakash Patel; reviewing and editing: Meenakshi Patel. All authors have approved the final version of the manuscript.

Corresponding author

Correspondence to Meenakshi Patel.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Communicated by M. Alice Maciel Tabosa, Jaimin R. Shah, Sharareh Senemar, and Nisarg Modi

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) 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

Patel, M., Patel, A., Desai, J. et al. Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations. AAPS PharmSciTech 25, 46 (2024). https://doi.org/10.1208/s12249-024-02763-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-024-02763-4

Keywords

Search

Navigation