Study Of Bioequivalence And Biowaiver Of Domestic Moxifloxacin Hydrochloride Tablets

Objective1 To study the bioequivalence of test(domestic drugs)and reference formulation(original drugs)of moxifloxacin hydrochloride.2 To study the feasibility of biowaiver of immediate release solid oral dosage forms containing moxifloxacin hydrochloride.Methods1 A hligh performance liquid chromatography-fluorescence detection method(HPLC-FLD)was developed and validated to determine the concentrations of moxifloxacin in human plasma.Twenty-four volunteers received a single dose of the test(Domestic pharma company)or reference(Bayer Pharma AG)formulation,then plasma samples were collected and determined by the HPLC-FLD method.By means of WinNonlin Ver 6.4 software,pharmacokinetic parameters were calculated using a non-compartmental mode.The log-transformed main pharmacokinetic parameters were compared by analysis of variance,and the 90% confidence intervals(90%CIs)of the test-to-reference geometric mean ratio(GMR)of AUC and Cmax were calculated to assess the bioequivalence.2 The moxifloxacin equilibrium solubility at pH 1~6.8 water-soluble medium was determined by shake-flask method and HPLC-FLD method.The permeability of moxifloxacin was determined by literature.And the dissolution of moxifloxacin hydrochloride tablets was determined by paddle method and HPLC-FLD method.According to the solubility and permeability of moxifloxacin hydrochloride,and the dissolution of moxifloxacin hydrochloride test and reference formulations,as well as the results of bioequivalence studies,combined with the excipients factors of moxifloxacin hydrochloride,the feasibility of biowaiver of immediate release solid oral dosage forms containing moxifloxacin hydrochloride was investigated.Results1 After administration of test and reference formulations under fasting condition,the pharmacokinetical parameters of moxifloxacin were as follows,Cmax were(4.41 ± 1.18)?g·mL-1 and(4.43 ± 1.07)?g·mL-1,Tmax were(1.16 ± 0.87)h and(1.21 ± 0.98)h,t1/2 were(13.40 ± 1.47)h and(13.44 ± 1.42)h,AUC0-t were(47.11 ± 5.81)?g·h·mL-1 and(46.89 ± 5.36)?g·h·mL-1,AUC0-? were(51.11 ± 6.63)?g·h·mL-1 and(50.92 ± 6.26)?g·h·mL-1,respectively.After administration of test and reference formulations under fed condition,the pharmacokinetical parameters of moxifloxacin were as follows,Cmax were(3.37 ± 0.774)?g·mL-1 and(3.64 ± 0.771)?g·mL-1,Tmax were(1.71±0.69)h and(1.88±0.68)h,t1/2 were(13.40 ± 1.44)h and(13.74 ± 1.31)h,AUC0-t were(43.39 ± 6.81)?g·h·mL-1 and(44.22 ± 6.92)?g·h·mL-1,AUC0-? were(47.30 ± 8.06)?g·h·mL-1 and(48.42 ± 8.18)?g·h·mL-1,respectively.The relative bioavailability of test and reference formulations under fasting and fed conditions of moxifloxacin were(100.51 ± 5.37)% and(98.2 ± 4.48)%,respectively.The main pharmacokinetic parameters of moxifloxacin were log-ransformed.The 90%CIs of the GMR of AUC0-t,AUC0-? and Cmax between the test and reference formulations fell within the limits of 80.00~125.00% under fasting and fed conditions,respectively.2 The D/S of moxifloxacin hydrochloride in the pH1~6.8 water-soluble medium at 37 ± 1 were ? all less than 250 mL.The absolute bioavailability of moxifloxacin was greater than 90%,therefore,moxifloxacin is highly permeable.The dissolution of moxifloxacin hydrochloride tablets were more than 85% in the 500 mL water-soluble medium with pH1.0,4.5 and 6.8 at 50 rpm.The excipients of moxifloxacin hydrochloride tablets in the study were within the does range specified by FDA,and would not affect the absorption of the drug.Conclusions1 The test formulation was proved to be bioequivalent to reference formulation both under fasting and fed conditions.2 Moxifloxacin hydrochloride was highly soluble and highly permeable,belonging to BCS?.Moxifloxacin hydrochloride test and reference formulations were very rapid dissolved.Excipients factors had little effect on the bioequivalence of moxifloxacin.A biowaiver for moxifloxacin hydrochloride test formulation could be considered acceptable..3 Biowaiver for other immediate release solid oral dosage forms containing moxifloxacin hydrochloride would be considered acceptable if the following conditions are met: 1)the dosage forms can be rapidly dissolved;2)excipients used in the preparations have little effect on absorption.