Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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

Electrospun Transdermal Patch for Contraceptive Hormone Delivery

Author(s): Mohammad Mofidfar and Mark R. Prausnitz*

Volume 16, Issue 6, 2019

Page: [577 - 583] Pages: 7

DOI: 10.2174/1567201816666190308112010

Abstract

Background: A transdermal patch for delivery of Levonorgestrel (LNG) can be used for long-acting contraception.

Objective: In this study, we designed and characterized a patch made of nonwoven electrospun microfibers comprised of Polycaprolactone (PCL) encapsulating LNG for slow release in a mineral oil matrix.

Methods and Results: Scanning electron microscopy showed uniform, randomly oriented PCL fibers with large interconnected voids filled with mineral oil. Thermogravimetric analysis indicated that LNG loaded into PCL fibers had thermal stability up to ~200°C. Differential Scanning Calorimetry suggested that LNG was dispersed in the electrospun fibers without interaction between the LNG and PCL, and without formation of drug crystals. Fourier Transform Infrared spectroscopy and X-ray diffraction results further supported the conclusion that there was no chemical drug–polymer interaction in LNGloaded fibers. Effective in vitro flux (i) from patches into mineral oil was 1.9 µgcm-2h-1, (ii) from mineral oil across porcine skin was 4.6 µgcm-2h-1 and (iii) from patches across porcine skin was 1.7 μgcm- 2h-1, indicating that transdermal delivery rate was controlled by a combination of the patch and the skin.

Conclusion: The LNG-loaded patches demonstrated steady delivery of LNG across skin for up to 5 days in vitro. With additional development, LNG-loaded electrospun PCL patches could be used for long-acting contraception.

Keywords: Transdermal drug delivery, long-acting contraceptive, levonorgestrel, polycaprolactone, electrospun fiber patch, contraceptive hormone delivery.

« Previous
Graphical Abstract

[1]
Sedgh, G.; Singh, S.; Hussain, R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud. Fam. Plann., 2014, 45(3), 301-314.
[http://dx.doi.org/10.1111/j.1728-4465.2014.00393.x] [PMID: 25207494]
[2]
Benagiano, G.; Gabelnick, H.; Brosens, I. Long-acting hormonal contraception. Womens Health (Lond), 2015, 11(6), 749-757.
[http://dx.doi.org/10.2217/whe.15.68] [PMID: 26626534]
[3]
Friend, D.R. Development of controlled release systems over the past 50years in the area of contraception. J. Control. Release, 2016, 240, 235-241.
[http://dx.doi.org/10.1016/j.jconrel.2015.12.043] [PMID: 26732558]
[4]
Creasy, G.W.; Abrams, L.S.; Fisher, A.C. Transdermal contraception. Semin. Reprod. Med., 2001, 19(4), 373-380.
[http://dx.doi.org/10.1055/s-2001-18645] [PMID: 11727179]
[5]
Galzote, R.M.; Rafie, S.; Teal, R.; Mody, S.K. Transdermal delivery of combined hormonal contraception: A review of the current literature. Int. J. Womens Health, 2017, 9, 315-321.
[http://dx.doi.org/10.2147/IJWH.S102306] [PMID: 28553144]
[6]
Tepper, N.K.; Dragoman, M.V.; Gaffield, M.E.; Curtis, K.M. Nonoral combined hormonal contraceptives and thromboembolism: A systematic review. Contraception, 2017, 95(2), 130-139.
[http://dx.doi.org/10.1016/j.contraception.2016.10.005] [PMID: 27771476]
[7]
Zamani, M.; Prabhakaran, M.P.; Ramakrishna, S. Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int. J. Nanomedicine, 2013, 8, 2997-3017.
[PMID: 23976851]
[8]
Goyal, R.; Macri, L.K.; Kaplan, H.M.; Kohn, J. Nanoparticles and nanofibers for topical drug delivery. J. Control. Release, 2016, 240, 77-92.
[http://dx.doi.org/10.1016/j.jconrel.2015.10.049] [PMID: 26518723]
[9]
Shi, Y.; Wei, Z.; Zhao, H.; Liu, T.; Dong, A.; Zhang, J. Electrospinning of ibuprofen-loaded composite nanofibers for improving the performances of transdermal patches. J. Nanosci. Nanotechnol., 2013, 13(6), 3855-3863.
[http://dx.doi.org/10.1166/jnn.2013.7157] [PMID: 23862418]
[10]
Shi, Y.; Li, Y.; Wu, J.; Wang, W.; Dong, A.; Zhang, J. A novel transdermal drug delivery system based on self-adhesive Janus nanofibrous film with high breathability and monodirectional water-penetration. J. Biomater. Sci. Polym. Ed., 2014, 25(7), 713-728.
[http://dx.doi.org/10.1080/09205063.2014.897596] [PMID: 24641249]
[11]
Blakney, A.K.; Krogstad, E.A.; Jiang, Y.H.; Woodrow, K.A. Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures. Int. J. Nanomedicine, 2014, 9(1), 2967-2978.
[http://dx.doi.org/10.2147/IJN.S61664] [PMID: 24971008]
[12]
Karande, P.; Mitragotri, S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim. Biophys. Acta, 2009, 1788(11), 2362-2373.
[http://dx.doi.org/10.1016/j.bbamem.2009.08.015] [PMID: 19733150]
[13]
Sharma, P.K.; Panda, A.; Pradhan, A.; Zhang, J.; Thakkar, R.; Whang, C.H.; Repka, M.A.; Murthy, S.N. Solid-state stability issues of drugs in transdermal patch formulations. AAPS PharmSciTech, 2018, 19(1), 27-35.
[http://dx.doi.org/10.1208/s12249-017-0865-3] [PMID: 28895101]
[14]
Watkinson, A.C.; Kearney, M.C.; Quinn, H.L.; Courtenay, A.J.; Donnelly, R.F. Future of the transdermal drug delivery market--have we barely touched the surface? Expert Opin. Drug Deliv., 2016, 13(4), 523-532.
[http://dx.doi.org/10.1517/17425247.2016.1130034] [PMID: 26646399]
[15]
Chaudhuri, K.R. Crystallisation within transdermal rotigotine patch: Is there cause for concern? Expert Opin. Drug Deliv., 2008, 5(11), 1169-1171.
[http://dx.doi.org/10.1517/17425240802500870] [PMID: 18976128]
[16]
Enis, I.Y.; Vojtech, J.; Sadikoglu, T.G. Alternative solvent systems for polycaprolactone nanowebs via electrospinning. J. Ind. Text., 2016, 47(1), 57-70.
[http://dx.doi.org/10.1177/1528083716634032]
[17]
Baer, E.; Wnek, G.E.; Mofidfar, M.; Wang, J. Polymer fiber scaffolds and uses thereof., 2017.https://www.google.com/patents/
[18]
Hillery, A.M.; Lloyd, A.W.; Swarbrick, J. Drug delivery and targeting for pharmacists and pharmaceutical scientists; In: CRC Press: London, 2001.
[19]
Yoshimoto, H.; Shin, Y.M.; Terai, H.; Vacanti, J.P. A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials, 2003, 24(12), 2077-2082.
[http://dx.doi.org/10.1016/S0142-9612(02)00635-X] [PMID: 12628828]
[20]
Cipitria, A.; Skelton, A.; Dargaville, T.R.; Dalton, P.D.; Hutmacher, D.W. Design, fabrication and characterization of PCL electrospun scaffolds-a review. J. Mater. Chem., 2011, 21(26), 9419-9453.
[http://dx.doi.org/10.1039/c0jm04502k]
[21]
Manoukian, O.S.; Arul, M.R.; Sardashti, N.; Stedman, T.; James, R.; Rudraiah, S.; Kumbar, S.G. Biodegradable polymeric injectable implants for long-term delivery of contraceptive drugs. J. Appl. Polym. Sci., 2018, 135(14), 46068.
[http://dx.doi.org/10.1002/app.46068] [PMID: 29430061]
[22]
Mofidfar, M.; Wang, J.; Long, L.; Hager, C.L.; Vareechon, C.; Pearlman, E.; Baer, E.; Ghannoum, M.; Wnek, G.E. Polymeric nanofiber/antifungal formulations using a novel co-extrusion approach. AAPS PharmSciTech, 2017, 18(6), 1917-1924.
[http://dx.doi.org/10.1208/s12249-016-0664-2] [PMID: 27858252]
[23]
Dhanaraju, M.D.; Jayakumar, R.; Vamsadhara, C. Influence of manufacturing parameters on development of contraceptive steroid loaded injectable microspheres. Chem. Pharm. Bull. (Tokyo), 2004, 52(8), 976-979.
[http://dx.doi.org/10.1248/cpb.52.976] [PMID: 15304994]
[24]
Buyuktimkin, N.; Buyuktimkin, S.; Rytting, J.H. Chemical means of transdermal drug permeation enhancement. Transdermal and Topical Drug Delivery Systems; Ghosh, T.K.; Pfister, W.R.; Yum, S; Eds.; Informa Health Care, 1997
[25]
Friend, D.R.; Catz, P.; Heller, J.; Okagaki, M. Transdermal delivery of levonorgestrel. IV: Evaluation of membranes. J. Pharm. Sci., 1989, 78(6), 477-480.
[http://dx.doi.org/10.1002/jps.2600780612] [PMID: 2503604]
[26]
Friend, D.R.; Catz, P.; Heller, J.; Okagaki, M. Transdermal delivery of levonorgestrel. V. Preparation of devices and evaluation in vitro. Pharm. Res., 1989, 6(11), 938-944.
[http://dx.doi.org/10.1023/A:1015937311711] [PMID: 2512569]
[27]
Friend, D.; Catz, P.; Heller, J. Simple alkyl esters as skin permeation enhancers. J. Control. Release, 1989, 9(1), 33-41.
[http://dx.doi.org/10.1016/0168-3659(89)90031-X]

Rights & Permissions Print Cite
Article Metrics
65
7
2
2
© 2024 Bentham Science Publishers | Privacy Policy