本文選題：鹽酸莫西沙星　切入點：藥代動力學(xué)　出處：《錦州醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的1、研究國產(chǎn)鹽酸莫西沙星片(受試制劑)與原研藥(參比制劑)的生物等效性。2、研究鹽酸莫西沙星普通口服固體制劑仿制藥生物豁免的可行性。方法1、建立高效液相色譜—熒光檢測法(HPLC-FLD)測定人血漿中莫西沙星濃度,并進行驗證;各24名健康中國男性志愿者分別于空腹和餐后口服受試制劑(國內(nèi)某制藥公司研制并生產(chǎn))和參比制劑(德國Bayer Pharma AG生產(chǎn)),采集血漿樣品,并采用已通過驗證的HPLC-FLD法測定血漿中莫西沙星的濃度;采用WinNonlin 6.4軟件,非房室模型方法計算志愿者口服受試制劑和參比制劑后莫西沙星的藥代動力學(xué)參數(shù),主要藥代動力學(xué)參數(shù)對數(shù)轉(zhuǎn)換后進行方差分析,90%置信區(qū)間法評價制劑間生物等效性。2、采用HPLC-FLD法和搖瓶法測定鹽酸莫西沙星原料藥在pH值1~6.8標準緩沖溶液中的平衡溶解度。通過文獻確定莫西沙星滲透性。采用HPLC-FLD法和槳法測定鹽酸莫西沙星片受試制劑和參比制劑在溶出介質(zhì)中的的溶出度。根據(jù)鹽酸莫西沙星的溶解性、滲透性,本課題中鹽酸莫西沙星片受試制劑和參比制劑的溶出度、及人體生物等效性研究結(jié)果,結(jié)合輔料因素探討鹽酸莫西沙星普通口服固體制劑仿制藥生物豁免的可行性。結(jié)果1、志愿者空腹口服受試制劑和參比制劑后血漿中的莫西沙星的cmax分別為(4.41±1.18)μg·ml-1和(4.43±1.07)μg·ml-1;tmax分別為(1.16±0.87)h和(1.21±0.98)h;t1/2分別為(13.40±1.47)h和(13.44±1.42)h;auc0-t分別為(47.11±5.81)μg·h·ml-1和(46.89±5.36)μg·h·ml-1;auc0-∞分別為(51.11±6.63)μg·h·ml-1和(50.92±6.26)μg·h·ml-1。志愿者餐后口服受試制劑和參比制劑后血漿中的莫西沙星的cmax分別為(3.37±0.774)μg·ml-1和(3.64±0.771)μg·ml-1;tmax分別為(1.71±0.69)h和(1.88±0.68)h;t1/2分別為(13.40±1.44)h和(13.74±1.31)h;auc0-t分別為(43.39±6.81)μg·h·ml-1和(44.22±6.92)μg·h·ml-1;auc0-∞分別為(47.30±8.06)μg·h·ml-1和(48.42±8.18)μg·h·ml-1。鹽酸莫西沙星受試制劑與參比制劑空腹給藥試驗的相對生物利用度f為(100.51±5.37)%,餐后給藥試驗的相對生物利用度f為(98.2±4.48)%。經(jīng)對數(shù)轉(zhuǎn)換后,志愿者空腹和餐后條件下口服受試制劑和參比制劑的auc0-t、auc0-∞和cmax幾何均數(shù)比值(gmr)的90%置信區(qū)間均在80.00%~125.00%的范圍內(nèi)。2、鹽酸莫西沙星原料藥在37±1℃,ph值1~6.8(0.1mol·l-1hcl和ph值為2.0、3.0、4.5、5.1、5.8、6.8的緩沖液)的水溶性介質(zhì)中最大劑量/溶解度比值(d/s)均小于250ml,具有高溶解性;根據(jù)已有文獻資料報道,鹽酸莫西沙星的絕對生物利用度大于90%,具有高滲透性;在50rpm轉(zhuǎn)速條件下,500ml溶出介質(zhì)(0.1mol·l-1hcl、ph值4.5緩沖介質(zhì)、ph值6.8緩沖介質(zhì))中,15min內(nèi)鹽酸莫西沙星片受試制劑和參比制劑的溶出度均達到標示量的85%以上;本課題中的鹽酸莫西沙星片受試制劑的輔料處方中輔料為固體制劑常用輔料且含量在fda規(guī)定的含量范圍內(nèi),不影響藥物的吸收。結(jié)論1、在空腹給藥與餐后給藥兩種試驗條件下,受試制劑與參比制劑均具有生物等效性。2、鹽酸莫西沙星為高溶解性、高滲透性藥物,屬于BCSⅠ類藥物;鹽酸莫西沙星片受試制劑和參比制劑均為非�？焖偃艹龅目诜腆w制劑;鹽酸莫西沙星片受試制劑的輔料成分對其生物等效性影響較小;該受試制劑推薦生物豁免。3、其他只含有鹽酸莫西沙星單一成分的普通口服固體制劑仿制藥上市,如果滿足下列要求,可以考慮豁免1)該制劑為快速溶出制劑2)處方中輔料對該制劑的吸收速率和吸收程度無顯著影響。
[Abstract]:Objective to study the domestic 1, Moxifloxacin Hydrochloride Tablets (sescs) and original drugs (reference preparation) the bioequivalence study of moxifloxacin hydrochloride.2, common oral solid preparation of generic biological immunity. The feasibility of method 1, the establishment of chromatography with fluorescence detection method of high performance liquid (HPLC-FLD) determination of moxifloxacin in human plasma, and the verification; 24 healthy male volunteers were China in fasting and postprandial oral test preparation (preparation and production of a pharmaceutical company in China) and reference preparation (German Bayer Pharma AG production), the collection of plasma samples, and the concentration in plasma was determined by HPLC-FLD method to verify the moxifloxacin; using WinNonlin 6.4 software non compartmental model, calculation method of tested preparation and reference pharmacokinetic parameters of moxifloxacin preparations after volunteers analyzed, the main pharmacokinetic parameters after logarithmic transformation, 90 % confidence interval method to evaluate the bioequivalence between the preparation of.2, using the HPLC-FLD method and shake flask method to determine the equilibrium solubility of 1~6.8 standard in the buffer solution of pH value in moxifloxacin hydrochloride raw medicine. Through the literature to determine the permeability of moxifloxacin. By using HPLC-FLD method and paddle method was Moxifloxacin Hydrochloride Tablets test and reference preparations in the dissolution medium the dissolution. Based on the solubility and permeability of moxifloxacin hydrochloride, Moxifloxacin Hydrochloride Tablets the test and reference preparations of dissolution, and the bioequivalence study results, combined with the discussion of common excipients of moxifloxacin hydrochloride oral solid preparation of generic biological immunity feasibility. The results of 1 volunteers were given orally by the test preparation and reference preparation of moxifloxacin in the plasma of Cmax were (4.41 + 1.18) g and ml-1 (4.43 + 1.07) g, ml-1; Tmax were (1.16 + 0.87) and H (1.21鹵0.98)h;t1/2鍒嗗埆涓，

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