Abstract
The objectives of this work were to prepare a 5 wt% lidocaine–diclofenac ionic liquid drug–loaded gelatin/poly(vinyl alcohol) transdermal patch using a freeze/thaw method and to evaluate its physicochemical properties, in vitro release of lidocaine and diclofenac, and stability test. The lidocaine–diclofenac ionic liquid drug was produced by the ion pair reaction between the hydrochloride salts of lidocaine and the sodium salts of diclofenac. The thermal properties of the final drug product were significantly changed from the primary drugs. The ionic liquid drug could be dissolved in water and mixed in a polymer solution. The resulting transdermal patch was then exposed to 10 cycles of freezing and thawing preparation at − 20°C for 8 h and at 25°C for 4 h, respectively. As a result, it was found that the lidocaine–diclofenac ionic liquid drug–loaded transdermal patch showed good physicochemical properties and could feasibly be used in pharmaceutical applications. The lidocaine–diclofenac ionic liquid drug was not affected by the properties of the transdermal patch due to the lack of chemical interaction between polymer base and drug. The high drug release values of both lidocaine and diclofenac were controlled by the gelatin/poly(vinyl alcohol) transdermal patch. The patch showed good stability over the study period of 3 months when kept at 4°C or under ambient temperature.
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Moniruzzaman M, Kamiya N, Goto M. Ionic liquid based microemulsion with pharmaceutically accepted components: formulation and potential applications. J Colloid Interface Sci. 2010;352(1):136–42. https://doi.org/10.1016/j.jcis.2010.08.035.
Brennecke JF, Maginn EJ. Ionic liquids: innovative fluids for chemical processing. AICHE J. 2001;47(11):2384–9. https://doi.org/10.1002/aic.690471102.
Mizuuchi H, Jaitely V, Murdan S, Florence AT. Room temperature ionic liquids and their mixtures: potential pharmaceutical solvents. Eur J Pharm Sci. 2008;33(4):326–31. https://doi.org/10.1016/j.ejps.2008.01.002.
Tomasz S, Michal Piotr M, Anna P. Ionic liquids: a new strategy in pharmaceutical synthesis. Mini-Rev Org Chem. 2012;9(2):203–8. https://doi.org/10.2174/157019312800604698.
Wilkes JS. A short history of ionic liquids—from molten salts to neoteric solvents. Green Chem. 2002;4(2):73–80. https://doi.org/10.1039/B110838G.
Shamshina JL, Berton P, Wang H, Zhou X, Gurau G, Rogers RD. Ionic liquids in pharmaceutical industry. Green techniques for organic synthesis and medicinal chemistry. 2018. pp. 539–77. https://doi.org/10.1002/9781119288152.ch20.
Marrucho IM, Branco LC, Rebelo LPN. Ionic liquids in pharmaceutical applications. Annu Rev Chem Biomol Eng. 2014;5(1):527–46. https://doi.org/10.1146/annurev-chembioeng-060713-040024.
Dobler D, Schmidts T, Klingenhöfer I, Runkel F. Ionic liquids as ingredients in topical drug delivery systems. Int J Pharm. 2013;441(1):620–7. https://doi.org/10.1016/j.ijpharm.2012.10.035.
Huddleston JG, Visser AE, Reichert WM, Willauer HD, Broker GA, Rogers RD. Characterization and comparison of hydrophilic and hydrophobic room temperature ionic liquids incorporating the imidazolium cation. Green Chem. 2001;3(4):156–64. https://doi.org/10.1039/B103275P.
Moniruzzaman M, Goto M. Ionic liquids: future solvents and reagents for pharmaceuticals. J Chem Eng Jpn. 2011;44(6):370–81. https://doi.org/10.1252/jcej.11we015.
Pernak J, Sobaszkiewicz K, Mirska I. Anti-microbial activities of ionic liquids. Green Chem. 2003;5(1):52–6. https://doi.org/10.1039/B207543C.
Moniruzzaman M, Tahara Y, Tamura M, Kamiya N, Goto M. Ionic liquid-assisted transdermal delivery of sparingly soluble drugs. Chem Commun. 2010;46(9):1452–4. https://doi.org/10.1039/B907462G.
Goindi S, Arora P, Kumar N, Puri A. Development of novel ionic liquid-based microemulsion formulation for dermal delivery of 5-fluorouracil. AAPS PharmSciTech. 2014;15(4):810–21. https://doi.org/10.1208/s12249-014-0103-1.
Moniruzzaman M, Tamura M, Tahara Y, Kamiya N, Goto M. Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: characterization and cytotoxicity evaluation. Int J Pharm. 2010;400(1):243–50. https://doi.org/10.1016/j.ijpharm.2010.08.034.
Zakrewsky M, Lovejoy KS, Kern TL, Miller TE, Le V, Nagy A, et al. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc Natl Acad Sci. 2014;111(37):13313–8. https://doi.org/10.1073/pnas.1403995111.
Zhang D, Wang H-J, Cui X-M, Wang C-X. Evaluations of imidazolium ionic liquids as novel skin permeation enhancers for drug transdermal delivery. Pharm Dev Technol. 2017;22(4):511–20. https://doi.org/10.3109/10837450.2015.1131718.
Jaitely V, Karatas A, Florence AT. Water-immiscible room temperature ionic liquids (RTILs) as drug reservoirs for controlled release. Int J Pharm. 2008;354(1):168–73. https://doi.org/10.1016/j.ijpharm.2008.01.034.
Bica K, Rijksen C, Nieuwenhuyzen M, Rogers RD. In search of pure liquid salt forms of aspirin: ionic liquid approaches with acetylsalicylic acid and salicylic acid. Phys Chem Chem Phys. 2010;12(8):2011–7. https://doi.org/10.1039/B923855G.
Miwa Y, Hamamoto H, Ishida T. Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid. Eur J Pharm Biopharm. 2016;102:92–100. https://doi.org/10.1016/j.ejpb.2016.03.003.
Berton P, Di Bona KR, Yancey D, Rizvi SAA, Gray M, Gurau G, et al. Transdermal bioavailability in rats of lidocaine in the forms of ionic liquids, salts, and deep eutectic. ACS Med Chem Lett. 2017;8(5):498–503. https://doi.org/10.1021/acsmedchemlett.6b00504.
Park HJ, Prausnitz MR. Lidocaine-ibuprofen ionic liquid for dermal anesthesia. AICHE J. 2015;61(9):2732–8. https://doi.org/10.1002/aic.14941.
Hough WL, Smiglak M, Rodríguez H, Swatloski RP, Spear SK, Daly DT, et al. The third evolution of ionic liquids: active pharmaceutical ingredients. New J Chem. 2007;31(8):1429–36. https://doi.org/10.1039/B706677P.
Maneewattanapinyo P, Suksaeree J. Development and validation of HPLC method for characterization of the acidic and basic drugs prepared into ionic liquid. Lat Am J Pharm. 2019;38(5):961–7.
Roy SD, Gutierrez M, Flynn GL, Cleary GW. Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design. J Pharm Sci. 1996;85(5):491–5. https://doi.org/10.1021/js950415w.
Heuschkel S, Goebel A, Neubert RHH. Microemulsions — modern colloidal carrier for dermal and transdermal drug delivery. J Pharm Sci. 2008;97(2):603–31. https://doi.org/10.1002/jps.20995.
Goebel ASB, Knie U, Abels C, Wohlrab J, Neubert RHH. Dermal targeting using colloidal carrier systems with linoleic acid. Eur J Pharm Biopharm. 2010;75(2):162–72. https://doi.org/10.1016/j.ejpb.2010.02.001.
Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70. https://doi.org/10.3390/pharmaceutics7040438.
Hassan CM, Peppas NA. Structure and applications of Poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. In: Chang JY, Godovsky DY, Han MJ, Hassan CM, Kim J, Lee B, et al., editors. Biopolymers PVA hydrogels, anionic polymerisation nanocomposites. Berlin Heidelberg: Springer; 2000. p. 37–65.
Hassan CM, Peppas NA. Structure and morphology of freeze/thawed PVA hydrogels. Macromolecules. 2000;33(7):2472–9. https://doi.org/10.1021/ma9907587.
Martínez YN, Cavello I, Hours R, Cavalitto S, Castro GR. Immobilized keratinase and enrofloxacin loaded on pectin PVA cryogel patches for antimicrobial treatment. Bioresour Technol. 2013;145:280–4. https://doi.org/10.1016/j.biortech.2013.02.063.
Gonzalez JS, Martínez YN, Castro GR, Alvarez VA. Preparation and characterization of polyvinyl alcohol–pectin cryogels containing enrofloxacin and keratinase as potential transdermal delivery device. Adv Mater Lett. 2016;7(8):640–5.
Ah Y-C, Choi J-K, Choi Y-K, Ki H-M, Bae J-H. A novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization. Int J Pharm. 2010;385(1-2):12–9. https://doi.org/10.1016/j.ijpharm.2009.10.013.
Cilurzo F, Minghetti P, Casiraghi A, Tosi L, Pagani S, Montanari L. Polymethacrylates as crystallization inhibitors in monolayer transdermal patches containing ibuprofen. Eur J Pharm Biopharm. 2005;60(1):61–6. https://doi.org/10.1016/j.ejpb.2005.02.001.
Jain P, Banga AK. Inhibition of crystallization in drug-in-adhesive-type transdermal patches. Int J Pharm. 2010;394(1–2):68–74. https://doi.org/10.1016/j.ijpharm.2010.04.042.
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Maneewattanapinyo, P., Yeesamun, A., Watthana, F. et al. Controlled Release of Lidocaine–Diclofenac Ionic Liquid Drug from Freeze-Thawed Gelatin/Poly(Vinyl Alcohol) Transdermal Patches. AAPS PharmSciTech 20, 322 (2019). https://doi.org/10.1208/s12249-019-1545-2
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DOI: https://doi.org/10.1208/s12249-019-1545-2