Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug.
Microemulsion systems composed of water, isopropyl myristate, PEG-8 caprylic/capric glycerides (Labrasol), and polyglyceryl-6 dioleate (Plurol Oleique), were investigated as potential drug delivery vehicles for an amphiphilic model drug (diclofenac diethylamine). Pseudo-ternary phase diagram of the investigated system, at constant surfactant/cosurfactant mass ratio (Km 4:1) was constructed at room temperature by titration, and the oil-to-surfactant/cosurfactant mass ratios (O/SC) that exhibit the maximum in the solubilization of water were found. This allowed the investigation of the continuous structural inversion from water-in-oil to oil-in-water microemulsions on dilution with water phase. Furthermore, electrical conductivity (sigma) of the system at Km 1:4, and O/SC 0.250 was studied, and the percolation phenomenon was observed. Conductivity and apparent viscosity (eta') measurement results well described colloidal microstructure of the selected formulations, including gradual changes during their formation. Moreover, sigma, eta', and pH values of six selected microemulsion vehicles which differ in water phase volume fraction (phi(w)) at the selected Km and O/SC values, were measured. In order to investigate the influence of the amphiphilic drug on the vehicle microstructures, each system was formulated with 1.16% (w/w) diclofenac diethylamine. Electrical conductivity, and eta' of the investigated systems were strongly affected by drug incorporation. The obtained results suggest that diclofenac diethylamine interacts with the specific microstructure of the investigated vehicles, and that the different drug release kinetics from these microemulsions may be expected. The investigated microemulsions should be very interesting as new drug carrier systems for dermal application of diclofenac diethylamine.
Djordjevic
Ljiljana
L
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia and Montenegro. girasole@ptt.yu
Primorac
Marija
M
Stupar
Mirjana
M
Krajisnik
Danina
D
D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002210:Caprylates / Q000737:chemistry*; D003652:Decanoic Acids / Q000737:chemistry*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D004553:Electric Conductivity; D004655:Emulsions / Q000737:chemistry; D005989:Glycerides; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008859:Microscopy, Polarization; D009829:Oleic Acids / Q000737:chemistry*; D009930:Organic Chemicals; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity; D014867:Water
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002210:Caprylates; D003652:Decanoic Acids; D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D009829:Oleic Acids; D009930:Organic Chemicals; D013501:Surface-Active Agents; C480531:polyglyceryl-6-dioleate; C440220:Labrasol; D014867:Water; D004008:Diclofenac; C031492:octanoic acid; D005990:Glycerol