title: Effect of microemulsions on transdermal delivery of citalopram: optimization studies using mixture design and response surface methodology.
abstract: The aim of this study was to evaluate the potential of microemulsions as a drug vehicle for transdermal delivery of citalopram. A computerized statistical technique of response surface methodology with mixture design was used to investigate and optimize the influence of the formulation compositions including a mixture of Brij 30/Brij 35 surfactants (at a ratio of 4:1, 20%-30%), isopropyl alcohol (20%-30%), and distilled water (40%-50%) on the properties of the drug-loaded microemulsions, including permeation rate (flux) and lag time. When microemulsions were used as a vehicle, the drug permeation rate increased significantly and the lag time shortened significantly when compared with the aqueous control of 40% isopropyl alcohol solution containing 3% citalopram, demonstrating that microemulsions are a promising vehicle for transdermal application. With regard to the pharmacokinetic parameters of citalopram, the flux required for the transdermal delivery system was about 1280 μg per hour. The microemulsions loaded with citalopram 3% and 10% showed respective flux rates of 179.6 μg/cm(2) and 513.8 μg/cm(2) per hour, indicating that the study formulation could provide effective therapeutic concentrations over a practical application area. The animal study showed that the optimized formulation (F15) containing 3% citalopram with an application area of 3.46 cm(2) is able to reach a minimum effective therapeutic concentration with no erythematous reaction.
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of China.
authors.forename: Chi-Te
authors.initials: CT
authors.lastname: Huang
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lin
authors.forename: Yaw-Sya
authors.initials: YS
authors.lastname: Fu
authors.forename: Yaw-Bin
authors.initials: YB
authors.lastname: Huang
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Tsai
authors.forename: Pao-Chu
authors.initials: PC
authors.lastname: Wu
mesh_terms: D019840:2-Propanol; D000279:Administration, Cutaneous; D000818:Animals; D015283:Citalopram / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D004890:Erythema / Q000139:chemically induced; D008297:Male; D015233:Models, Statistical; D053758:Nanoparticles; D000077423:Polidocanol; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000077423:Polidocanol; D015283:Citalopram; D011092:Polyethylene Glycols; C515901:Brij 35; D019840:2-Propanol
keywords: citalopram; microemulsion; transdermal delivery systems
references.citation: Eur J Pharm Sci. 2012 Sep 29;47(2):497-505
references.pmid: 22820033
references.citation: Clin Exp Dermatol. 1990 Jul;15(4):267-72
references.pmid: 2208776
references.citation: AAPS PharmSciTech. 2009;10(4):1093-103
references.pmid: 19757079
references.citation: Int J Dermatol. 2012 Jul;51(7):859-63
references.pmid: 22715835
references.citation: J Microencapsul. 2013;30(1):81-92
references.pmid: 22746546
references.citation: Drugs. 1991 Mar;41(3):450-77
references.pmid: 1711447
references.citation: Eur J Pharm Sci. 2002 Sep;16(4-5):237-46
references.pmid: 12208453
references.citation: Int J Pharm. 2008 Aug 6;360(1-2):184-90
references.pmid: 18541394
references.citation: Int J Pharm. 2010 Mar 30;388(1-2):257-62
references.pmid: 20060453
references.citation: Int J Pharm. 2012 Jul 1;430(1-2):18-25
references.pmid: 22465631
references.citation: Int J Pharm. 2001 Oct 9;228(1-2):161-70
references.pmid: 11576778
references.citation: Eur J Pharm Biopharm. 2009 Nov;73(3):391-8
references.pmid: 19660544
references.citation: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Jun;149(1):169-72
references.pmid: 16170406
references.citation: Molecules. 2012 May 18;17(5):5972-87
references.pmid: 22609787
references.citation: Clin Ther. 2000 Dec;22(12):1525-32
references.pmid: 11192143
references.citation: Drug Deliv. 2011 Jan;18(1):19-25
references.pmid: 20726811
references.citation: J Pharm Sci. 2010 Nov;99(11):4603-15
references.pmid: 20845459
references.citation: Drug Deliv. 2008 Sep;15(7):465-9
references.pmid: 18712624
references.citation: J Pharm Sci. 2011 Feb;100(2):580-93
references.pmid: 20669331
references.citation: J Liposome Res. 2012 Dec;22(4):270-8
references.pmid: 22676370
references.citation: J Pharm Sci. 1996 Feb;85(2):138-43
references.pmid: 8683437
references.citation: Drug Dev Ind Pharm. 2013 Aug;39(8):1207-16
references.pmid: 22804226
references.citation: J Pharm Sci. 2008 Feb;97(2):603-31
references.pmid: 17696162
references.citation: Dermatology. 1994;189(2):146-51
references.pmid: 8075442
references.citation: Biomed Chromatogr. 2010 Oct;24(10):1052-8
references.pmid: 20352615
references.citation: Int J Pharm. 2001 Jun 4;220(1-2):63-75
references.pmid: 11376968
references.citation: Drugs Today (Barc). 2007 Jun;43(6):361-77
references.pmid: 17612708
references.citation: Eur J Pharm Biopharm. 2008 Feb;68(2):446-51
references.pmid: 18191759
references.citation: Gen Hosp Psychiatry. 2012 Sep-Oct;34(5):541-5
references.pmid: 22534401
references.citation: Int J Pharm. 2001 Jun 19;221(1-2):23-34
references.pmid: 11397564
references.citation: AAPS PharmSciTech. 2008;9(3):762-8
references.pmid: 18563577
references.citation: Int J Pharm. 2008 May 1;355(1-2):285-92
references.pmid: 18243604
references.citation: AAPS PharmSciTech. 2010 Jun;11(2):976-85
references.pmid: 20517714
references.citation: Eur J Pharm Sci. 2012 Sep 29;47(2):297-304
references.pmid: 22750416
references.citation: Int J Pharm. 2003 Mar 26;254(2):99-107
references.pmid: 12623186
references.citation: Drug Deliv. 2004 Mar-Apr;11(2):97-105
references.pmid: 15200008
references.citation: J Colloid Interface Sci. 2009 Feb 15;330(2):443-8
references.pmid: 19038395
references.citation: Pharm Res. 2003 Feb;20(2):264-9
references.pmid: 12636166
references.citation: Int J Pharm. 2004 Aug 6;280(1-2):241-51
references.pmid: 15265563
references.citation: Int J Pharm. 2006 Sep 14;321(1-2):117-23
references.pmid: 16876972
references.citation: Eur J Pharm Biopharm. 2007 Nov;67(3):699-706
references.pmid: 17537622
references.citation: J Chromatogr B Biomed Sci Appl. 2001 May 5;755(1-2):279-85
references.pmid: 11393715
references.citation: Int J Pharm. 2002 Sep 5;244(1-2):21-31
references.pmid: 12204562
references.citation: Curr Drug Deliv. 2010 Oct;7(4):329-33
references.pmid: 20695844
references.citation: Int J Pharm. 2008 Jul 9;359(1-2):220-7
references.pmid: 18472233
references.citation: J Clin Psychiatry. 2012 Sep;73(9):e28
references.pmid: 23059160
references.citation: J Clin Psychiatry. 2012;73 Suppl 1:25-30
references.pmid: 22951239