噁拉戈利钠片的制备及体内外评价

Preparation and in vitro-in vivo Evaluation of Elagolix Sodium Tablets

该研究制备了噁拉戈利钠自研片,并以溶出相似因子f_(2)为判断指标,优化了活性药物成分(API)粒径、干法制粒过筛筛网孔径以及片剂硬度等3个关键制剂工艺参数。结果显示,当API的粒径[d(0.9)]为250μm、干法制粒过筛筛网的孔径为1.4 mm、片剂硬度为80 N时,自研片与参比制剂的体外释放行为一致。随后,该研究采用平行人工膜渗透分析(PAMPA)法中相关的渗透参数和在Beagle犬体内的药物动力学特征来研究自研片的生物等效性。结果表明,自研片和参比制剂的渗速率分别为8.6988和8.1616μg·mL^(-1)·min^(-1),膜渗透性分别为2.24×10^(-4)和2.10×10^(-4)cm/s,自研片的置信区间为100.82%~104.54%;两者的药动学参数均无统计学差异(P>0.05),自研片的相对生物利用度为(95.4±8.69)%,与参比制剂生物等效。

In this study,elagolix sodium self-developed tablets were formulated by optimizing three key formulation process parameters,namely the particle size of active pharmaceutical ingredient(API),the aperture of sieve screen in the dry granulation process,and the tablet hardness.The similarity factor(f_(2))values between the dissolution curves of the self-developed and reference tablets were calculated as a criterion for evaluation.The results indicated that when the API particle size[d(0.9)]was 250μm,the aperture of sieve screen was 1.4 mm,and the tablet hardness was 80 N,the in vitro dissolution behavior of the self-developed tablets was similar to that of the reference formulations.Subsequently,bioequivalence was investigated using relevant permeation parameters from the parallel artificial membrane permeation assay(PAMPA)and pharmacokinetic characteristics in Beagle dogs.The results revealed that the permeation rates of the self-developed tablets and the reference formulations were 8.6988 and 8.1616μg·mL^(-1)·min^(-1)respectively,with membrane permeabilities of 2.24×10^(-4)and 2.10×10^(-4)cm/s.The confidence interval for the self-developed tablets ranged from 100.82%to 104.54%.There was no statistically significant difference in the pharmacokinetic parameters between the two groups(P>0.05).The relative bioavailability of the self-developed tablets was found to be(95.4±8.69)%,demonstrating the bioequivalence with the reference formulations.