A novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization.
A monolithic drug-in-adhesive (MDIA) type patch containing meloxicam (MX) was designed with an acrylic adhesive, a solubility modulator increasing MX solubility, and enhancers. MDIA patches having one adhesive layer between the backing and the release liner give high productivity and improve patient compliance. The biggest problem to prepare MDIA patch including MX was poor solubility of MX. In this research, solubility modulators to increase solubility of MX and acrylic adhesives and skin permeation enhancers were investigated through solubility tests, in vitro skin permeation tests, and stability tests. Consequently, the composition of sodium methoxide (SM), an acrylic adhesive containing poly(vinyl pyrrolidone) blocks (MAS683), polyoxyethylene cetylether (BC-2), and diisopropanolamine (DIPA) made it possible for MX to be contained in an adhesive layer at a concentration of as much as 15 wt% without MX crystal and with high skin permeation over 400 microG/cm(2). Finally, the patch formulation containing MX (MX-patch) selected through our in vitro study was characterized by in vivo using an animal study to acquire pharmacokinetic (PK) parameters and to confirm the anti-inflammatory efficacy of MX-patch. In the animal study, MX-patch was compared with a commercially available piroxicam patch (PX-patch). The amount of MX delivered from MX-patch to the skin surface was believed to be higher than the amount of MX diffused from the skin tissue to circulatory system because the plasma concentration of MX continuously increased up to 32 h, the end time of PK study, although the patch samples were detached at 24 h. PX-patch produced a C(max) at 8 h. MX-patch showed better significant efficacy than PX-patch in adjuvant arthritis model.
Ah
Young-Chang
YC
Amorepacific Co., R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 449-729, Republic of Korea.
Choi
Jin-Kyu
JK
Choi
Yang-Kyu
YK
Ki
Han-Moi
HM
Bae
Joon-Ho
JH
D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000382:microbiology; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004195:Disease Models, Animal; D004304:Dosage Forms; D004339:Drug Compounding; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005079:Excipients / Q000737:chemistry; D005620:Freund's Adjuvant; D000077239:Meloxicam; D051379:Mice; D008812:Mice, Hairless; D009161:Mycobacterium; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy / Q000382:microbiology; D010539:Permeability; D010894:Piroxicam / Q000008:administration & dosage; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013843:Thiazines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014014:Tissue Adhesives / Q000737:chemistry
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D005079:Excipients; D013843:Thiazines; D013844:Thiazoles; D014014:Tissue Adhesives; D010894:Piroxicam; D002351:Carrageenan; D005620:Freund's Adjuvant; D011205:Povidone; D000077239:Meloxicam