Influence of n-octenylsuccinate starch on in vitro permeation of sodium diclofenac across excised porcine cornea in comparison to Voltaren ophtha.
The influence of different n-octenylsuccinate starch (AS) formulations, i.e. AS solutions and an AS stabilized emulsion system, on the in vitro corneal permeation behaviour of sodium diclofenac (DfNa) was investigated and compared to the commercial product Voltaren ophtha (VO). Although saturation concentrations of DfNa achieved with polyoxethylene-35-castor oil (POC), which is the solubilizing additive in VO, are higher than those achieved with AS at varying pH values, it was found that AS solutions yield higher DfNa permeation rates than VO or a POC solution. However, permeation is extremely reduced with rising AS concentrations or AS emulsions. Neither pH value (6.5 or 7.4) nor presence of preservative seem to have an impact on permeation activity. In order to assess possible cytotoxic effects of the preparations investigated, red blood cell haemolysis studies were performed with different preparations containing DfNa. None of the tested AS formulations showed significantly high haemolytic data. On the other hand the high in vitro haemolysis obtained with VO is primarily based on an osmotic effect caused by boric acid.
Baydoun
Luma
L
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany.
Müller-Goymann
Christel C
CC
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D004008:Diclofenac / Q000493:pharmacokinetics* / Q000633:toxicity; D004339:Drug Compounding; D004655:Emulsions; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009883:Ophthalmic Solutions; D009994:Osmolar Concentration; D010539:Permeability; D013213:Starch / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D013552:Swine; D014783:Viscosity
D000277:Adjuvants, Pharmaceutic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D009883:Ophthalmic Solutions; D013386:Succinates; D004008:Diclofenac; D013213:Starch