Effects Of Delivery Route And Dosage Form On The Pharmacokinetics Of Two Crystal Forms Of Rifampicin

Different crystals of the same drug after its oral administration could show thedifference in bioavailability and clinical effects. However, the earlier research on thebioavailability after oral administration only involved suspension and dry powder.After transformation of delivery route and the usage of dosage form except forsuspension, whether the differences in the bioavailability between the polymorphs ofsuspension is still existed, has not reported. Consequently, I and II polymorphs ofrifampicin are selected as model drugs to discuss the effect of factors of dosage form(suspension and capsule) and delivery route (oral and rectal administration) on thebioavailability of rifampicin polymorphs.Firstly, I and II polymorphs of rifampicin prepared in different solvent systems byrecrystallization technique were characterized by different analytical methods. Thecrystalline structure of rifampicin polymorphs was analyzed using p-XRD. Thecharacteristic peaks of rifampicin form I and form II appeared at13.62,14.38and9.90,11.042θ, respectively. As observed from DSC thermogram, form I directlydecomposed by sharp exotherm at253～265℃. Form II showed melting endotherm at183～200℃immediately followed by recrystallization to form I, and fnallydecomposed at247～266℃. Form I showed uniform rod and block like particles andform showed uniform rod like particles from SEM photomicrographs.Based on the establishment of HPLC applied to the analysis of rifampicin in theblood drug concentration, pharmacokinetics of rifampicin polymorphs was studiedafter oral and rectal administration of self-prepared suspension and capsule ofrifampicin.(1) After oral administration of rifampicin suspension I, the mainpharmacokinetics parameters calculated were as follows: Tmaxwas3.150h, Cmaxwas10.43μg/mL, AUC0-twas52.47h*mg/mL. After rectal administration of rifampicinsuspension I, the main parameters: Tmaxwas4.175h, Cmaxwas11.65μg/mL, AUC0-twas67.25h*mg/mL.(2) After oral administration of rifampicin capsule I, the mainparameters: Tmaxwas1.925h, Cmaxwas10.30μg/mL, AUC0-twas46.20h*mg/mL.After rectal administration of rifampicin capsule I, the main parameters: Tmaxwas3.925h, Cmaxwas9.150μg/mL, AUC0-twas53.91h*mg/mL.(3) After oral administration of rifampicin suspension II, the main parameters: Tmaxwas2.975h,Cmaxwas13.68μg/mL, AUC0-twas82.60h*mg/mL. After rectal administration ofrifampicin suspension II, the main parameters: Tmaxwas4.025h, Cmaxwas8.950μg/mL, AUC0-twas52.54h*mg/mL.(4) After oral administration of rifampicincapsule II, the main parameters: Tmaxwas2.075h, Cmaxwas8.375μg/mL, AUC0-twas56.25h*mg/mL. After rectal administration of rifampicin capsule II, the mainparameters: Tmaxwas4.125h, Cmaxwas7.425μg/mL, AUC0-twas47.37h*mg/mL.After oral administration of rifampicin, form II showed a higher bioavailabilitythan form I. However, after rectal administration of two crystal forms of rifampicin,form I exhibited a higher bioavailability than form II. The bioavailability ofrifampicin suspension was higher than capsule, which was not affected by deliveryroutes.