Preparation optimization and the pharmacokinetics and the evaluation in vivo of 6-(4-chlorophenoxy)-tet-razolo[5,1-a]phthalazine nanoemulsions
OBJECTIVE To prepare 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine(Q808-NE),optimize its prepara-tion process and conduct in vivo and in vitro evaluations.METHODS Encapsulation rate(EE),drug loading(DL)and cen-trifugal stability constant(K)were utilized as observation indices.Single factor assays,Plackett-Burman design(PBD)and Box-Behnken design(BBD)were employed for optimizing the preparation process of Q808 nanoemulsion.Q808 nanoemulsion was evaluated for physicochemical characterization,pharmacokinetics and in vivo distributions.RESULTS The optimal preparation parameters were as follows:aqueous phase ratio was 83.33％and stirring conditions of 400 r·min-1,40 ℃ and 2 h.Aqueous phase was added at a rate of 2 seconds per drop.Ratio of oil phase(oleic acid)to mixed emulsifier(5∶4 ratio of Polysorbate 80 to Poloxamer 188)was 3∶7 and ratio of emulsifier to co-emulsifier 3∶1.Average particle size,PDI and Zeta-potential were(38.54±2.22)nm,0.26±0.01 and(-27.63±0.96)mV.Solubility in water was 1 046.11 folds higher than that of Q808.Oral relative bioavailability of Q808-NE was 230.83％.And in vivo distribution test revealed that relative uptake rate in brain was 2.91,indi-cating a certain trend of brain targeting.CONCLUSION Q808-NE has been prepared effectively.It may boost the solubility and bioavailability of the drug.Brain targeting is feasible.Thus it provides a novel option for subsequent dosing.
6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazinepharmacokineticsin vivo distributionnanotargeting
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