title: Formulation optimization of an indomethacin-containing photocrosslinked polyacrylic acid hydrogel as an anti-inflammatory patch.
abstract: Photocrosslinked polyacrylic acid hydrogel, made from polyacrylic acid (PAA) modified with 2-hydroxyethyl methacrylate (HEMA), is a promising candidate adhesive for dermatological patches. In this study, we investigated the further availability of hydrogel as an adhesive for dermatological patches using a hydrogel containing indomethacin (IDM) as a model anti-inflammatory patch. From an orthogonal experimental study, we clarified the relationships between formulation factors and characteristics of model formulation. Formulations with a lower degree of swelling were prepared by increasing the degree of HEMA modification and the addition of Tween 80. Apparent permeation rate was increased by addition of L-menthol and Tween 80. A tendency for higher HEMA modification to be accompanied by the prolongation of the lag time of IDM was observed. To obtain an applicable anti-inflammatory patch, we conducted a formulation optimization study using a novel optimization method, a response-surface method incorporating multivariate spline interpolation (RSM-S). Consequently, a highly functional anti-inflammatory patch in terms of its adhesive properties and bioavailability was successfully obtained. Since a wide range of functions can be fully controlled by manipulating the formulation factors, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches.
authors.affiliation: Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo, 142-8501, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Onuki
authors.forename: Koichi
authors.initials: K
authors.lastname: Isowa
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D008297:Male; D010777:Photochemistry; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003432:Cross-Linking Reagents; D020100:Hydrogels; C006903:carbopol 940; D007213:Indomethacin
references.citation: Int J Pharm. 2008 Feb 12;349(1-2):47-52
references.pmid: 17723282
references.citation: J Pharm Sci. 2008 Jan;97(1):331-9
references.pmid: 17722113
references.citation: Eur J Pharm Biopharm. 2000 Jul;50(1):27-46
references.pmid: 10840191
references.citation: J Biomed Mater Res. 2002 Feb;59(2):233-45
references.pmid: 11745558
references.citation: Biomaterials. 2003 Nov;24(24):4337-51
references.pmid: 12922147
references.citation: J Control Release. 2004 Jan 8;94(1):101-14
references.pmid: 14684275
references.citation: J Control Release. 2004 May 31;97(1):91-9
references.pmid: 15147807
references.citation: Pharmazie. 2004 May;59(5):392-5
references.pmid: 15212308
references.citation: Chem Pharm Bull (Tokyo). 1992 Nov;40(11):3097-9
references.pmid: 1477927
references.citation: J Pharm Sci. 1994 Sep;83(9):1367-72
references.pmid: 7830256
references.citation: J Pharm Sci. 1997 Dec;86(12):1369-73
references.pmid: 9423148
references.citation: Biomaterials. 1998 Jul;19(13):1119-36
references.pmid: 9720896
references.citation: J Control Release. 1999 Nov 1;62(1-2):161-70
references.pmid: 10518647
references.citation: J Control Release. 2005 Nov 28;108(2-3):331-40
references.pmid: 16202471
references.citation: Biol Pharm Bull. 2006 Jan;29(1):146-9
references.pmid: 16394528
references.citation: Adv Drug Deliv Rev. 2006 Nov 30;58(12-13):1379-408
references.pmid: 17081649
references.citation: Chem Pharm Bull (Tokyo). 2007 Apr;55(4):586-93
references.pmid: 17409553
references.citation: J Control Release. 2007 Aug 16;121(1-2):81-90
references.pmid: 17617489
references.citation: J Control Release. 2007 Sep 26;122(2):119-34
references.pmid: 17719120
references.citation: J Pharm Sci. 2008 Jan;97(1):318-30
references.pmid: 17683058
references.citation: Chem Pharm Bull (Tokyo). 2006 Apr;54(4):481-4
references.pmid: 16595949