Preparation And Characterization Of Prednisolone Acetate Solid Lipid Nanoprticles

Solid lipid nanoparticles(SLN) is a promising an alternative carrier system with solid,biodegradable lipid as drug carriers, diameters ranging between 50-1000 nanometers,which has the advantages of high physical stability,more entrapped efficiency(EE),controlled drug release and sustained release, more bioavailability comparing to other transdermal preparations. It also has the advantages of low speed of leakage,low cytotoxity,large scale production etc.The objective of this thesis was to study of prednisolone acetate loaded solid lipid nanoparticles.First, the EE of drug was determined spectrophotometrically by Ultraviolet absorbance at 243nm after the free drug molecules was separated from PA-SLN on a sephadexG-50 minicolumn.We studied the mechanic and influencing factors of EE, according to the results of the study before fomulation designing.Compared to the passive loading methods, the Solvent emulsification evaporation―Solidifying method was developed to prepare PA-SLN suspension.The optimal formulation was obtained by orthogonal experiment design. the optimal formulation of EE up to 79.4±1.2%,and DL was 3.8±0.1%.The quality of the PA-SLN was evaluated (Zetasizer 3000HSA and electroscopy ,etc) .The results showed the SLN suspension was welled distrubuted with a mean diameter of 176.4nm, a Zeta potential of -30.8mv, Results of the stability experiments indicated that the PA-SLN suspension could be kept stable at 4℃for 30 days.A pilot investigation on in vitro drug release was carried on and the curve fitting method was used to find the drug release eqution,it showed tally with Higuchi equation,and 0～4h showed tally with Zero order kinetics,10～120h showed tally with One order kinetics.An HPLC method for determination of the contents of Prednisolone Acetate in Wistar rats plasma was established.Pharmacokinetic parmaeters and relative bioavailbility were evaluated in Wistar rats with injection of prednisolone acetate suspension as reference standard.The data were managed using 3p87 pharmacokinetic program,the results indicated that the SLN preparation had the good role of sustained release and its relative bioavailability was higher than 100%.