The Development Of Dispersible Tablet Of Ganciclovir And The Pharmacokinetics Study In Dog

Ganciclovir is widely used in the treatment of cytomegalovirus(CMV) infection, especially to AIDS patients. However, ganciclovir is good dissolutable in fat and poor dissolutable in water, absorbed badly by taking orally and showes low bioavailability, only 6—9%. We developed the dispersible tablets of ganciclovir in order that it can increase the dissolubility rate and disintegrating rate ,and it be absorbed quickly and absolutely, so the bioavailability of ganciclovir will be increased.The basic prescription and preparation technology was initially defined by the study about formulation screening and technology optimizing , based on the pharmacy rule as indicator. Orthogonal project was employed to screen the prescriptions which based on the study of mono-factor experiment. The optimized ganciclovir dispersed tablets include: ganciclovir125mg, MCC 100mg, PVPP 25mg, magnesium stearate 2mg, water as lubricant.The quality study of the dispersible tablet of ganciclovir was done.The main componets included that the identification methods were set up(colour effection and UV method),the UV method and the HPLC method were established for the content determination of ganciclovir, TLC was established for the examing of the correlated material.Further more,the dispersible tablet of ganciclovir examing method of the dissolubility was founded. In-vitro dissolution test showed that the optimized ganciclovir dispersed tablets could completely disintegrated within 30s and the dissolution rate of ganciclovir was over 90% after 6 minutes. The in-vitro dissolubility of the optimized dispersed tablet is better than those of common tablet and capsule(P<0.01). The initial stability study showed that light and high temperature had little effect on the dispersible tablet , but humidity had some obvious effects on the appearance and content of the dispersible tablet.The results suggest that the dispersible tablet of ganciclovir should be packed in moistureproof material and preserved under cold,dry enviroment.The pharmacokinetics and bioavailability study of the dispersible tablet of ganciclovir in dogs was made.The HPLC method which determinates the ganciclovir concentration inthe dog serum was established. By a series of study of precision and accuracy, The method was tested and proved to be suited for studying pharmacokinetics in dogs.The ganciclovir capsule was used as the reference preparation,the pharmacokinetics study of the dispersible tablet of ganciclovir in the dog and the bioequivalence evaluation were made by two preparations two cycles crossing trial desigh.The results of the pharmacokinetics trial in six dogs indicates that the dispersible tablet and capsule in vivo single dosage tests mainly fits the one-compartment. Cmax of ganciclovir of the two preparations were 51.62±7.37ug/ml and 46.06+ 10.37ug/ml.Tmax were 3.42+1.22h and 3.08±0.58h. AUC0-24 were 311.31 + 69.40mg/L-h and 278.73 +62.95mg/L-h.The bioavailability between the two preparations were 111.69%.The evaluation result of bioequivalence showed that the dispersible tablet and the capsule is bioequivalent.