Development of Poly (Methyl vinyl ether-alt-maleic acid) Microneedles for Transdermal Delivery of Atorvastatin Calcium

Author(s): Pablo S. Castañeda, Clara L. Domínguez Delgado, Isabel M.R. Cruz, Luz M.M. Contreras, Eva M.M. Trinidad, Miriam L. Cervantes, José J. Escobar-Chávez*

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 9 , 2020


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Graphical Abstract:


Abstract:

Aims: Biodegradable polymeric microneedles containing atorvastatin calcium were developed in order to improve the percutaneous absorption of the drug, useful for the treatment of hypercholesterolemia.

Background: The use of physical enhancers like microneedles have shown good results to increase the delivery of drugs through the skin, the use of microneedles has very important advantages for transdermal drug delivery, for example, they are painless, easy to use and safe, they increase time interval of drug activity, dose, and reductions in adverse reactions, they also offer, the facility to remove the system instantly of the skin.

Objective: Develop polymer microneedles loaded with a calcium atorvastatin and evaluate them by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, postwetting- bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies to demonstrate the use of microneedles atorvastatin is able to cross the skin.

Methods: The microneedles were made with poly (methyl vinyl ether-alt-maleic acid) as biodegradable polymer using the technique of casting in solution in a mold. After solidification these microneedles were characterized by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), bioadhesion, post-wetting-bioadhesion, breaking strength, drug release test and in vitro percutaneous absorption studies.

Results: In general, the performances were satisfactory for optimal formulation in terms of DSC with no interactions between drug and excipients, SEM shows microneedles with a conical shape, bioadhesion of 1570 g.f, post wetting-bioadhesion of 1503.4 g.f, breaking strength of 1566.7g.f that is sufficient to disrupt Stratum corneum, good drug release and a flux of 33.4 μg/cm2*h with a tLag of 15.14 h for the in vitro percutaneous absorption.

Conclusion: The results indicate that it is possible to generate microneedles to increase the percutaneous absorption of calcium atorvastatin transdermally, with the potential to be used as an alternative to the oral route for the treatment of dyslipidemias.

Keywords: Microneedles, poly (methyl vinyl ether-alt-maleic acid), atorvastatin calcium, human skin, physical penetration enhancers, transdermal drug delivery.

[1]
Serrano-Castañeda, P.; Escobar-Chávez, J.J. Arroyo Vázquez, J.; Rodríguez-Cruz I. M.; Melgoza Contreras, L.M. Pravastatin transdermal patch: Effect of the formulation and length of microneedles on in- vitro percutaneous absorption studies. Iran. J. Pharm. Res., 2019.
[http://dx.doi.org/10.22037/IJPR.2019.1100914]
[2]
Serrano Castañeda, P.; Escobar Chávez, J.J.; Torres Aguado, A.; Rodríguez Cruz, I.M.; Melgoza Contreras, L.M. Desing and evaluation of a transdermal patch with atorvastatin. Farmacia, 2017, 65(6), 908-916.
[3]
Mahmoud, M.O.; Aboud, H.M.; Hassan, A.H.; Ali, A.A.; Johnston, T.P. Transdermal delivery of atorvastatin calcium from novel nanovesicular systems using polyethylene glycol fatty acid esters: Ameliorated effect without liver toxicity in poloxamer 407-induced hyperlipidemic rats. J. Control. Release, 2017, 254, 10-22.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.039] [PMID: 28344015]
[4]
Serrano-Castañeda, P.; Escobar-Chávez, J.J.; Rodríguez-Cruz, I.M.; Melgoza, L.M.; Martínez-Hernández, J. Microneedles as enhancer of drug absorption through the skin and applications in medicine and cosmetology. J. Pharm. Pharm. Sci., 2018, 21(1), 73-93.
[http://dx.doi.org/10.18433/jpps29610] [PMID: 29510800]
[5]
Yang, M.; Gu, Y.; Tang, X.; Wang, T.; Liu, J. Advancement of lipid-based nanocarriers and combination application with physical penetration technique. Curr. Drug Deliv., 2019, 16(4), 312-324.
[http://dx.doi.org/10.2174/1567201816666190118125427] [PMID: 30657039]
[6]
Prausnitz, M.R. Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev., 2004, 56(5), 581-587.
[http://dx.doi.org/10.1016/j.addr.2003.10.023] [PMID: 15019747]
[7]
Escobar-Chavéz, J.J. Current technologies to increase the transdermal delivery of drugs, Vol 1Bentham Science Publishers Ltd.: Dubai, U.A.E., 2010.
[8]
Escobar-Chavéz, J.J. Current Technologies to Increase the Transdermal Delivery of DrugsBentham Science Publishers Ltd.: Dubai, U.A.E., 2016.
[9]
Benson, H.A.E.; Grice, J.E.; Mohammed, Y.; Namjoshi, S.; Roberts, M.S. Topical and transdermal drug delivery: From simple potions to smart technologies. Curr. Drug Deliv., 2019, 16(5), 444-460.
[http://dx.doi.org/10.2174/1567201816666190201143457] [PMID: 30714524]
[10]
Yang, S.; Feng, Y.; Zhang, L.; Chen, N.; Yuan, W.; Jin, T. A scalable fabrication process of polymer microneedles. Int. J. Nanomedicine, 2012, 7, 1415-1422.
[PMID: 22457598]
[11]
Wang, M.; Hu, L.; Xu, C. Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing. Lab Chip, 2017, 17(8), 1373-1387.
[http://dx.doi.org/10.1039/C7LC00016B] [PMID: 28352876]
[12]
Harrison, J.S.; Ounaies, Z. Encyclopedia of Polymer Science and Technology; John Wiley & Sons: USA, 2002.
[13]
McCarron, P.A.; Donnelly, R.F.; Zawislak, A.; Woolfson, A.D.; Price, J.H.; McClelland, R. Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions. Int. J. Pharm., 2005, 293(1-2), 11-23.
[http://dx.doi.org/10.1016/j.ijpharm.2004.11.035] [PMID: 15778040]
[14]
Gill, H.S.; Prausnitz, M.R. Pocketed microneedles for drug delivery to the skin. J. Phys. Chem. Solids, 2008, 69(5-6), 1537-1541.
[http://dx.doi.org/10.1016/j.jpcs.2007.10.059] [PMID: 20648232]
[15]
Quinn, H.L.; Bonham, L.; Hughes, C.M.; Donnelly, R.F. Design of a dissolving microneedle platform for transdermal delivery of a fixed-dose combination of cardiovascular drugs. J. Pharm. Sci., 2015, 104(10), 3490-3500.
[http://dx.doi.org/10.1002/jps.24563] [PMID: 26149914]
[16]
Comisión permanente de la Farmacopea de los Estados Unidos Mexicanos. Farmacopea de los Estados Unidos Mexicanos, 9th ed; Secretaria de Salud: México, 2008.
[17]
Serrano Castañeda, P.; Escobar Chávez, J.J.; Morales Hipólito, A.; Domínguez Delgado, C.; Abrego Reyes, V. Microagujas y Transcutol® como promotores de la penetración transdérmica de sibutramina formulada en parche transdérmico. Rev. Cuba. Farm., 2013, 47(3), 289-299.
[18]
Serrano-Castañeda, P. Uso de microagujas para hacer más eficiente el paso de clorhidrato de sibutramina a través de piel humana formulado en parches transdérmicos de una matriz polimérica de quitosán con Transcutol.Bachelor Thesis, FESC UNAM: México, 2011.
[19]
Dash, S.; Murthy, P.N.; Nath, L.; Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm., 2010, 67(3), 217-223.
[PMID: 20524422]
[20]
Chung, K.; Wu, C.; Malawe, E. Glass transition temperatures of Poly (Methyl Vinyl Ether-Co-Maleic Anhydride) (PMVEMA) and Poly (Methyl Vinyl Ether-Co-Maleic Acid) (PMVEMAC) and the kinetics of dehydration of PMVEMAC by thermal analysis. J. Appl. Polym. Sci., 1990, 41, 793-803.
[http://dx.doi.org/10.1002/app.1990.070410326]
[21]
Barzegar, M.; Garjani, A.; Javadzadeh, Y.; Hamishehkar, H.; Jahangiri, A.; Adibkia, K. Pharmacological and histological examination of atorvastatin-PVP K30 solid dispersion. Powder Technol., 2015, 286, 538-545.
[http://dx.doi.org/10.1016/j.powtec.2015.08.047]
[22]
Choudhary, A.; Rana, A.; Aggarwal, G.; Kumar, V.; Zakir, F. Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability. Acta Pharm. Sin. B, 2012, 2(4), 421-428.
[http://dx.doi.org/10.1016/j.apsb.2012.05.002]
[23]
Jahangiri, A.; Barzegar-Jalali, M.; Garjani, A.; Javadzadeh, Y.; Hamishehkar, H.; Asadpour-Zeynali, K.; Adibkia, K. Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions. Eur. J. Pharm. Sci., 2016, 82, 21-30.
[http://dx.doi.org/10.1016/j.ejps.2015.11.007] [PMID: 26551750]
[24]
Davis, S.P.; Landis, B.J.; Adams, Z.H.; Allen, M.G.; Prausnitz, M.R. Insertion of microneedles into skin: Measurement and prediction of insertion force and needle fracture force. J. Biomech., 2004, 37(8), 1155-1163.
[http://dx.doi.org/10.1016/j.jbiomech.2003.12.010] [PMID: 15212920]
[25]
Holowka, E.; Bhatia, S.K. Drug Delivery Materials Design and Clinical Perspective; Springer: USA, 2014.
[26]
Islam, S.; Rahman, Z.; Khatun, M.; Ahmed, J.; Reza, S. Studies on bio-adhesion of matrix tablets: II. comparison on bio-adhesion strength and release profiles of theophylline anhydrous and its sodium glycinate salt. Dhaka Univ. J. Pharm. Sci., 2011, 10(1), 1-7.
[PMID: 21905029]
[27]
Woodley, J. Bioadhesion: New possibilities for drug administration? Clin. Pharmacokinet., 2001, 40(2), 77-84.
[http://dx.doi.org/10.2165/00003088-200140020-00001] [PMID: 11286325]
[28]
Wong, T.W.; Wahab, S.; Anthony, Y. Effects of microwave on drug release property of poly(methyl vinyl ether-co-maleic acid) matrix. Drug Dev. Ind. Pharm., 2007, 33(7), 737-746.
[http://dx.doi.org/10.1080/03639040601015513] [PMID: 17654022]
[29]
Prausnitz, M.; Elias, P.; Franz, T.; Schmuth, M.; Tsai, J.; Menon, G.; Holleran, W.; Feingold, K. Skin barrier and transdermal drug delivery; Medical therapy section 19, USA, 2012.
[30]
Martínez-Hernández, J. Liberación transdérmica de Pravastatina Sódica formulada en microagujas poliméricas biodegradables; Bachelor Thesis, FESC UNAM: México, 2014. September.
[31]
Kim, Y.C.; Park, J.H.; Prausnitz, M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev., 2012, 64(14), 1547-1568.
[http://dx.doi.org/10.1016/j.addr.2012.04.005] [PMID: 22575858]
[32]
Leveque, N.; Makki, S.; Hadgraft, J.; Humbert, P. Comparison of Franz cells and microdialysis for assessing salicylic acid penetration through human skin. Int. J. Pharm., 2004, 269(2), 323-328.
[http://dx.doi.org/10.1016/j.ijpharm.2003.09.012] [PMID: 14706244]


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VOLUME: 21
ISSUE: 9
Year: 2020
Page: [852 - 861]
Pages: 10
DOI: 10.2174/1389201021666200217103302
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