Viscosity of hydrogel pharmaceutical products and the rate of diffusion of ibuprofen hydrotropic binding through model phase boundary in vitro.
The aim of the carried out investigations was to establish relation between rheological parameters of market hydrogels containing ibuprofen and therapeutic agent diffusion coefficient dependent on their prescription. An attempt was made to estimate rheological parameters (structural viscosity, kinetics of volatile components loss) effect on pharmaceutical availability Q and the order of the process of mass exchange through artificial and natural phase boundary. Designed for skin anti-inflammatory hydrogels containing ibuprofen in the form of hydrotropic adduct with lysine (Ibufen, Dolofast), in the form of sodium salt (Nurofen) and in the form of molecular fragmentation of acidic form (Dolgit) were tested. The rate of volatile components loss was estimated with gravimetric method, viscosity measurements of therapeutic agents aqueous solutions were performed with Ubbelohde viscosimeter, while hydrogels rheological parameters - with cone-plate digital rheometer. The rate of ibuprofen penetration through phase boundary (Viscing dialysis membrane and pig perimastoid dermis) into dialysis fluid was determined in vitro. The kinetics of this process was monitored by measuring electric conduction Deltalambda = f(t) of model dialysis fluid. Viscometric measurements of aqueous solutions of ibuprofen lysine salt and ibuprofen sodium salt, by determining boundary viscosity gradient GLL(eta) and calculation of hydrodynamic radius Robs, enabled the applicative solution of Einstein-Smoluchowski equation (D = kT/6Pi r eta) and the estimation of structural value of therapeutic agent diffusion coefficient. Tracing the dependence between diffusion coefficient and shear rate enabled to recognize the preferences of preparations to the process of mass exchange on the phase boundary. An association was confirmed between the determined and calculated rheological parameters and the process of mass exchange on phase boundary through selected dialysis membranes. Mass exchange on phase boundary was found to be the derivative of the process of diffusion and its quantitative aspect depends on the kind of the applied membrane (it is the function of the quantity of statistically distributed pores on the unit of its surface [cm2]). Ibuprofen penetration through an artificial and natural phase boundary is complex. Its mechanism is between the kinetics of "0" and "II" order. The quantitative differentiation of the process of mass exchange between hydrotropic ibuprofen forms: ibuprofen lysine salt > ibuprofen sodium salt > ibuprofen in the form of acid molecule results from the carried out experimental study.
Zgoda
Marian Mikołaj
MM
Department of Drug Form Technology, Applied Pharmacy Faculty, Medical University in Lodz. mmzgoda@pharm.am.lodz.pl
Kołodziejska
Justyna
J
Nachajski
Michał Jakub
MJ
D000327:Adsorption; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D020405:Dermis / Q000378:metabolism; D004058:Diffusion; D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000493:pharmacokinetics*; D007052:Ibuprofen / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008954:Models, Biological; D012212:Rheology; D012867:Skin; D013552:Swine; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007052:Ibuprofen