title: Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.
abstract: Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
authors.forename: Biswadip
authors.initials: B
authors.lastname: Sinha
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India. biswajit55@yahoo.com.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Mukherjee
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry*; D004048:Diethylamines / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014783:Viscosity; D055815:Young Adult
chemical_list: D000179:Acrylates; D004048:Diethylamines; D005079:Excipients; C492578:carbopol 71G; D004008:Diclofenac; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011142:Polyvinyl Alcohol
keywords: anti-inflammatory; cadaver skin; nanosize dispersion; permeation enhancement; transdermal