title: Permeation enhancement of ketoprofen using a supersaturated system with antinucleant polymers.
abstract: Permeation enhancement of ketoprofen (KP) from supersaturated systems and the effects of antinucleant polymers on both stability and permeation of supersaturated KP were investigated using silicone membrane as a skin model. The supersaturation was prepared by the cosolvent technique with water and propylene glycol (PG). Saturated solubility of KP in water/PG cosolvent increased markedly with an increase in PG percentage. The time-profiles of the cumulative amount of released KP from supersaturated solutions through the membrane increased linearly, and this KP flux had a significant correlation with the degree of saturation (DS) in 80 : 20, 60 : 40, 50 : 50, and 40 : 60 (v/v) water/PG cosolvent systems. The influence of 1% solutions of antinucleant polymers, hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), and sodium carboxymethylcellulose (SCMC) on the DS and the stability of supersaturated KP was examined in 60 : 40 (v/v) water/PG cosolvent. The remaining DS for 24 h after mixing the solvents increased in the presence of HPMC and SCMC but not PVP. In the presence of SCMC, the physical stability of supersaturated KP was higher, however, the KP flux was lower than that in the control and in the presence of the other polymers. In conclusion, the supersaturation system can be applied to achieve higher transmembrane permeation of KP, and appropriate antinucleant polymers such as HPMC can optimize the physical stability and permeability of KP.
authors.affiliation: Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: Usanee
authors.initials: U
authors.lastname: Kumprakob
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
authors.forename: Isao
authors.initials: I
authors.lastname: Adachi
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium; D002851:Chromatography, High Pressure Liquid; D065347:Hypromellose Derivatives; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008567:Membranes, Artificial; D008747:Methylcellulose / Q000031:analogs & derivatives; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011205:Povidone; D011409:Propylene Glycols; D012995:Solubility; D012997:Solvents; D014867:Water
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008567:Membranes, Artificial; D010592:Pharmaceutic Aids; D011409:Propylene Glycols; D012997:Solvents; D014867:Water; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D007660:Ketoprofen; D011205:Povidone; D002266:Carboxymethylcellulose Sodium