Preparation And Evaluation Of Enteric-coated Pristinamycin Capsules With Enhanced Bioavailability

Objective:Pristinamycins have strong antibacterial activity and own a wide spectrum of activity.However,due to their poor solubilities in water and instabilities against acid and base,their oral bioavailabilities are not favourable.In order to improve the oral bioavailabilities of pristinamycins,we prepared pristinamycin I_A/II_A nanosuspensions enteric capsules and pristinamycin I_A/II_A cyclodextrin inclusion capsules.Methods:High pressure homogenization method was used in the preparation of pristinamycin I_A/II_A nanosuspensions.In vitro dissolution profiles of pristinamycin I_A/II_A were investigated in pristinamycin nanosuspension capsule dissolution test.Oral bioavailabilities and pharmacokinetic parameters were investigated in pristinamycin nanosuspension enteric capsule pharmacokinetic study.Saturated solution method was used in the preparation of pristinamycin I_A/II_A cyclodextrin inclusions.In vitro dissolution profiles of pristinamycin I_A/II_A were investigated in pristinamycin cyclodextrin inclusion capsule dissolution test.Oral bioavailabilities and pharmacokinetic parameters were investigated in pristinamycin cyclodextrin inclusion enteric capsule pharmacokinetic study.Results:The particle sizes of pristinamycin I_A/II_A nanosuspension lyophilized powder were 568.42±80.26nm and 470.35±74.92nm,respectively.Cumulative dissolution rates of pristinamycin I_A/II_A in nanosuspension capsule were 90.77%and 78.22%,respectively.Oral bioavailabilities of pristinamycin I_A/II_A in nanosuspension enteric capsule were 158.27%and 109.22%,respectively.The inclusion rates of pristinamycin I_A/II_A cyclodextrin inclusions were37.02%and 42.75%,respectively.Cumulative dissolution rates of pristinamycin I_A/II_A in cyclodextrin inclusion capsule were 85.27%and77.28%,respectively.Oral bioavailabilities of pristinamycin I_A/II_A in cyclodextrin inclusion enteric capsule were 192.22%and 162.98%,respectively.Conclusion:Enteric capsules containing pristinamycin nanosuspension or pristinamycin cyclodextrin inclusion nanosuspension could both improve the dissolution rates and oral bioavailabilities of pristinamycin I_A/II_A significantly compared with conventional dosage forms.