title: Formulation optimization and stability study of transdermal therapeutic system of nicorandil.
abstract: The aim of this research investigation was to fabricate acrylate-based stable transdermal therapeutic system (TTS) of nicorandil, which could deliver drug through transdermal route. Monolithic TTS was fabricated in pressure sensitive adhesives (PSAs)--(a) terpolymer (PSA1) of 2-ethylhexyl acrylate, methyl methacrylate, and acrylic acid, (b) copolymer (PSA2) of 2-ethylhexyl acrylate, methyl methacrylate, acrylic acid, and vinyl acetate, and (c) Eudragit E100 pressure sensitive adhesive (PSA3). To enhance the flux of nicorandil, skin permeation enhancer N-methyl-2-pyrrolidone (NMP) was investigated at different concentrations (0.05-5%) in PSAs. Fabricated TTS was evaluated for in-vitro release and skin permeation through guinea pig skin. Maximum flux of nicorandil was observed from Eudragit E100 based TTS and kept for stability study at refrigeration, 25 degrees C/30% RH and 30 degrees C/60% RH. Patches were evaluated for various physicochemical parameters. Formulation was observed to be relatively more stable at refrigeration. Shelf life of the formulation was found to be 270, 270, and 30 days at refrigeration, 25 degrees C/30% RH and 30 degrees C/60% RH conditions, respectively. Nicorandil could be successfully derived from Eudragit E100 based TTS, but attention needs to be given to improve its chemical stability in formulation.
authors.affiliation: University Department of Chemical Technology, Pharmaceutical Division, University of Mumbai, Matunga, Mumbai 400 019, India.
authors.forename: Dnyanesh N
authors.initials: DN
authors.lastname: Tipre
authors.forename: Pradeep R
authors.initials: PR
authors.lastname: Vavia
mesh_terms: D000179:Acrylates; D000269:Adhesives; D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D020108:Nicorandil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids; D011759:Pyrrolidines / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000179:Acrylates; D000269:Adhesives; D005079:Excipients; D011109:Polymethacrylic Acids; D011759:Pyrrolidines; D014665:Vasodilator Agents; C038300:methylmethacrylate-methacrylic acid copolymer; D020108:Nicorandil