目的 制備他達拉非片并考察其體內(nèi)外釋藥特性。方法 以溶出度為評價指標(biāo)，篩選他達拉非片各輔料用量及包衣增重。用相似因子（f₂）法比較自制制劑與參比制劑在0.5% SDS溶液、含0.5% SDS的0.1 mol/L的鹽酸溶液、含0.5% SDS的pH 4.5醋酸鈉緩沖液、含0.5% SDS的pH 6.8磷酸鹽緩沖液中溶出曲線的相似性。比較二者在Beagle犬體內(nèi)的藥動學(xué)特征。結(jié)果 他達拉非片處方為他達拉非20 mg、乳糖50M 227.625 mg、羥丙基纖維素L 10.5 mg、交聯(lián)羧甲基纖維素鈉19.6 mg、SDS 0.525 mg、微晶纖維素M102 70 mg、硬脂酸鎂1.75 mg，包衣增質(zhì)量范圍2%～4%。自制與參比制劑在4種溶出介質(zhì)中的f₂均大于65，二者體外溶出行為相似。2種制劑在Beagle體內(nèi)的藥動學(xué)參數(shù)AUC_0~t、C_max、t_max均無顯著性差異，自制他達拉非片的相對生物利用度為（101.67±8.99）%。結(jié)論 成功制備他達拉非片，其體外溶出和體內(nèi)藥動學(xué)行為與參比制劑相似。

Objective To prepare Tadalafil tablets and investigate its in vitro-in vivo release characteristics. Methods Using dissolution degree as index,to screen the amount of each excipient and the coating weight gain. f₂ similarity factor method was used to compare the similarity of dissolution curves between self-made preparation and reference preparation in 0.5%SDS solution, 0.1 mol/L hydrochloric acid solution containing 0.5% SDS, pH 4.5 sodium acetate buffer containing 0.5%SDS, and pH6.8 phosphate buffer containing 0.5% SDS.To compare the pharmacokinetic characteristics of the two preparations in beagle body. Results The formulation of tadalafil tablets was tadalafil 20 mg, 227.625 mg lactose 50M, 10.5 mg hydroxypropyl cellulose L, croscarmellose sodium 19.6 mg, SDS 0.525 mg, 70 mg microcrystalline cellulose M102, and magnesium stearate 1.75 mg, and the coating weight gain ranged from 2% to 4%.The similarity factor (f₂) of the self-made preparation and the reference preparation was greater than 65 in the four dissolution media, and the dissolution behavior of the two preparations was similar in vitro. There were no significant differences in pharmacokinetic parameters AUC_0-t, C_max and t_max. The relative bioavailability of self-made tadalafil tablets was (101.67 ±8.99)%. Conclusions Tadalafil tablets were successfully prepared, and its in vitro dissolution and in vivo pharmacokinetic behavior were similar to reference preparations.

R944.4

國家手性制藥工程技術(shù)研究中心資助項目（2016GGH4528）